The effect of hypoxia on epithelial-to-mesenchymal transition and microbiome composition in the invertebrate model organism Daphnia magna

Emile Clappaert
Persbericht

Watervlooien als nieuwe proefdieren in de strijd tegen kanker?

‘Een wat?’ Bij de meeste mensen aan wie ik mijn thesisonderwerp uit de doeken doe, komt deze vraag als eerste naar boven. ‘Een watervlo’, vertel ik dan, ‘is een kleine kreeftachtige die in zoet water voorkomt en leeft van algen en andere voedingsstoffen die het uit het water filtert.’ Met zijn ene oog, antennen en ietwat plompe lichaamsbouw heeft het niet meteen een hoge aaibaarheidsfactor. Toch kan dit kleine waterorganisme een rol spelen in toekomstig kankeronderzoek en het gebruik van andere proefdieren zoals muizen verminderen.

Watervlooi

Uitzaaien om te overleven

Kankercellen zijn echte energieverslinders. Energie die ze nodig hebben om hun snelle celgroei te kunnen volhouden. Om in hun grote vraag naar energie te kunnen voorzien worden grote hoeveelheden zuurstof en voedingsstoffen via het bloed aangeleverd naar de tumor. Hiervoor kan de tumor zelfs zijn eigen bloedvatenstelsel vormen door bloedvatcellen aan te trekken. Deze bloedvaten zijn echter slecht gemaakt en zullen slechts een klein deel van de tumor van bloed voorzien. Daarom blijven grote delen achter zonder voldoende energietoevoer. Door de stress die dit tekort veroorzaakt zullen de kankercellen zich genoodzaakt zien de originele tumor te verlaten en zich op andere voedselrijke plaatsen in het lichaam te vestigen. Dit kolonisatieproces wordt het uitzaaien van de tumor of metastase genoemd. Dit gaat vandaag nog steeds gepaard met een lage levensverwachting voor de patiënt. Daarom is het heel belangrijk om het mechanisme achter de uitzaaiingen te begrijpen om op die manier het proces te kunnen tegenhouden.

Eén van de eerste stappen waarbij de kankercellen zich losmaken van de originele tumor is het zich omvormen van een stevig verankerde of epitheliale kankercel naar een losse, zich vrij voortbewegende of mesenchymale kankercel. Deze overgang wordt de epitheliale-naar-mesenchymale transitie (EMT) genoemd en is een geconserveerd en omkeerbaar biologisch proces. In normale omstandigheden komt dit enkel voor tijdens de ontwikkeling van het embryo om de juiste cellen op de juiste plaats in het lichaam te krijgen. Daarnaast komt het ook voor tijdens het genezen van een wonde, waarbij de omliggende cellen zich reorganiseren om de wonde te dichten. Bij kanker zal dit proces echter misbruikt worden, geactiveerd door een hele reeks factoren zoals zuurstofgebrek, toxische stoffen of groeifactoren.

Proces

Nood aan een goed proefdier

Tot op vandaag zijn de experimenten op EMT in modelorganismen (in vivo) schaars en werden ze voornamelijk uitgevoerd in celculturen (in vitro). Omdat een goed in vivo model voor EMT nog steeds ontbreekt, introduceerden we in het labo de watervlo (Daphnia magna). Dit zoetwaterschaaldier wordt al decennialang gebruikt in ecologisch onderzoek en veroverde recent ook zijn plaats in het biomedische veld. De voordelen van Daphnia, zoals hun korte levenscyclus, vele nakomelingen, ongeslachtelijke voortplanting en het ontbreken van ethische beperkingen, maken het gebruik ervan interessant in kankeronderzoek. Indien we erin slagen om Daphnia als testorganisme op de biomedische wereldkaart te zetten, zou dit kunnen leiden tot het verminderen van het gebruik van gewervelde dieren zoals muizen, ratten en konijnen.

Watervlooien op hoogtestage

In mijn masterthesis werden twee experimenten uitgevoerd om EMT uit te lokken in Daphnia. In het eerste stelden we de watervlooien bloot aan een laag zuurstofgehalte om de zuurstofarme situatie in de tumor na te bootsen. Deze blootstelling leidde tot de productie van hemoglobine, een molecule dat de zuurstofopname verhoogt, waardoor onze watervlooien rood kleurden. Dit is vergelijkbaar met de verhoogde aanmaak van rode bloedcellen tijdens hoogtestages van topsporters, waar er ook minder zuurstof beschikbaar is. Tijdens het tweede experiment testten we de effecten van toxische stoffen op het activeren van EMT in Daphnia. Hiervoor voegden we toxische ééncellige algen toe, Microcystis aeruginosa. Deze algen produceren een krachtig gif, microcystine, dat al eerder in celculturen EMT heeft kunnen uitlokken.

Op vaste tijdstippen werd nagegaan of bepaalde EMT-gelinkte genen meer of minder werden geactiveerd in Daphnia. Een éénduidig resultaat werd hiervoor niet gevonden maar het lijkt erop te wijzen dat EMT niet voorkomt in Daphnia noch onder invloed van zuurstofgebrek noch door het toxische microcystine. Om die reden introduceren we de hypothese dat deze zoetwaterorganismen waarschijnlijk een beschermingsmechanisme hebben ontwikkeld dat EMT tegengaat. Dit kan te wijten zijn aan het feit dat de watervlooien ook in de natuur aan beide omstandigheden worden blootgesteld. Evolutionair gezien zou het best kunnen dat er een mechanisme is ontstaan dat de watervlooien beschermt tegen de schadelijke effecten die door deze condities worden uitgelokt. Verder onderzoek zal moeten uitwijzen op welke manier de watervlooien zich beschermen tegen het voorkomen van EMT. Dit zou zelfs kunnen leiden tot bevindingen die ons verder kunnen helpen in het ontwikkelen van therapieën tegen EMT en kankeruitzaaiingen. Dat is echter nog verre toekomstmuziek.

Hulp uit onverwachte hoek?

Ten slotte voerden we ook een kleinschalig experiment uit om de invloed van zuurstofgebrek op de samenstelling van de darmbacteriën of het microbioom in de Daphnia te onderzoeken. Darmbacteriën zijn vandaag een 'hot topic' in de geneeskunde en het is mogelijk dat het microbioom een rol speelde in de waargenomen bescherming tegen zuurstofgebrek in de watervlo. Na twee weken blootstelling aan lage zuurstofgehaltes werd er een duidelijke verschuiving waargenomen in de soortensamenstelling van de verzameling bacteriën in de darmen van de Daphnia. Een grootschalige studie op langere termijn is echter vereist om meer resultaten te krijgen van de invloed van de lage zuurstofgehaltes op de samenstelling van de bacteriën.

Hoe Daphnia zich kan wapenen tegen de activatie van EMT onder invloed van zuurstofgebrek en het toxische microcystine, is de vraag waarmee ik mijn thesis afsluit. Toekomstig onderzoek, waarbij een eventuele rol van de darmbacteriën wordt overwogen, zal hopelijk meer uitsluitsel brengen omtrent deze interessante observatie. Hoewel er zich nog veel vragen aandienen en nog veel verder onderzoek vereist is, kan er toch worden geconcludeerd dat de kleine Daphnia magna een rol kan spelen in toekomstig kankeronderzoek.

Bibliografie

 

1. Abreu, M. T., Peek, R. M. (2014). Gastrointestinal Malignancy and the Microbiome. Gastroenterology, 146(6), 1534-46.

2. Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M., Nieto, M. A. (2009). Epithelial-mesenchymal transitions: The importance of changing cell state in development and disease. Journal of Clinical Investigation, 119(6), 1438–49.

3. Apprill, A., McNally, S., Parsons, R., Weber, L. (2015). Minor revision to V4 region SSU rRNA 806R gene primer greatly increases detection of SAR11 bacterioplankton. Aquatic Microbial Ecology, 75, 129–37.

4. Aragonés, J., Schneider, M., Van Geyte, K., Fraisl, P., Dresselaers, T., Mazzone, M., Dirkx, R., Zacchigna, S., Lemieux, H., Jeoung, N. H., et al. (2008). Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nature Genetics, 40(2), 170–80.

5. Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J. Campbell, B. J., Abujamel, T., Dogan, B., Rogers, A B., et al. (2012). Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota. Science, 338, 120-23.

6. Asselman, J., De Coninck, D. I. M., Beert, E., Janssen, C. R., Orsini, L., Pfrender, M. E., Decaestecker, E., De Schamphelaere, K. A. C. (2017). Bisulfite Sequencing with Daphnia Highlights a Role for Epigenetics in Regulating Stress Response to Microcystis through Preferential Differential Methylation of Serine and Threonine Amino Acids. Environmental Science & Technology, 51(2), 924-31.

7. Au, S. H., Storey, B. D., Moore, J. C., Tang, Q., Cheng, Y.-L., Javaid, S., Sarioglu, A. F., Sullivan, R., Madden, M. W., O’Keefe, R., et al. (2016) Clusters of circulating tumor cells traverse capillary-sized vessels. PNAS, 113(18), 4947–52.

8. Barrallo-Gimeno, A., Nieto, M. A. (2005). The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development (Cambridge, England), 132(14), 3151–61.

9. Boulay, J. L., Dennefeld, C., Alberga, A. (1987). The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers. Nature, 330(6146), 395-8.

10. Broihier, H. T., Moore, L. A., Van Doren, M., Newman, S., Lehmann, R. (1998) zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila. Development, 125(4), 655-66.

11. Bruning, U., Cerone, L., Neufeld, Z., Fitzpatrick, S. F., Cheong, A., Scholz, C. C., Simpson, D. A., Leonard, M. O., Tambuwala, M. M., Cummins, E. P., et al. (2011). MicroRNA-155 Promotes Resolution of Hypoxia-Inducible Factor 1 alpha Activity during Prolonged Hypoxia. Molecular and Cellular Biology, 31(19), 4087-96.

12. Burns, C. W. (1969). Relation Between Filtering Rate, Temperature, and Body Size in Four Species of Daphnia. Limnology and Oceanography, 14(5), 693-700.

13. Callahan, B. J., Sankaran, K., Fukuyama, J. A., McMurdie, P. J., Holmes, S. P. (2016). Bioconductor Workflow for Microbiome Data Analysis: from raw reads to community analyses. F1000Research, 5, 1492.

14. Callens, M., Macke, E., Muylaert, K., Bossier, P., Lievens, B., Waud, M., Decaestecker, E. (2016). Food availability affects the strength of mutualistic host–microbiota interactions in Daphnia magna. ISME, 10(4), 911–20.

15. Campos, A., Vasconcelos, V. (2010). Molecular mechanisms of microcystin toxicity in animal cells. International Journal of Molecular Sciences, 11(1), 268–87.

16. Cane, G., Ginouvès, A., Marchetti, S., Buscà, R., Pouysségur, J., Berra, E., Hofman, P., Valérie, V.-C. (2010). HIF-1a mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour. Cellular Microbiology, 12(5), 640-53.

17. Carmeliet, P., Jain, R. K. (2011). Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nature Reviews. Drug Discovery,10, 417-27.

18. Castellone, M. D., Teramoto, H., Williams, B. O., Druey, K. M., Gutkind, J. S. (2005). Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310, 1504–10.

19. Cavadas, M. A. S., Mesnieres, M., Crifo, B., Manresa, M. C., Selfridge, A. C., Scholz, C. C., Cummins, E. P., Cheong, A., Taylor, C. T. (2015). REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia. Scientific Reports, 5, 17851.

20. Chaffer, C. L., Thompson, E. W., Williams, E. D. (2007). Mesenchymal to epithelial transition in development and disease. Cells, Tissues, Organs, 185(1-3), 7–19.

21. Chang, H., Kim, N., Park, J. H., Nam, R. H., Choi, Y. J., Park, S. M., Choi, Y. J., Yoon, H., Shin, C. M., Lee, D. H. (2015). Helicobacter pylori Might Induce TGF‐β‐Mediated EMT by Means of cagE. Helicobacter, 20(6), 438-48.

22. Cheung, M. Y., Liang, S., Lee, J. (2013). Toxin-producing cyanobacteria in freshwater: a review of the problems, impact on drinking water safety, and efforts for protecting public health. Journal of Microbiology (Seoul, Korea), 51(1), 1–10.

23. Cobaleda, C., Pérez-Caro, M., Vicente-Dueñas, C., Sánchez-García, I. (2007). Function of the zinc-finger transcription factor SNAI2 in cancer and development. Annual Review of Genetics, 41, 41–61.

24. Colbourne, J.K., Pfrender, M.E., Gilbert, D., Thomas, W.K., Tucker, A., Oakley, T.H. Tokishita, S., Aerts, A., Arnold, G., Basu, M., et al. (2011). The ecoresponsive genome of Daphnia pulex. Science, 331(6017), 555-61.

25. Crea, F., Clermont, P. L., Parolia, A., Wang, Y., Helgason, C. D. (2014). The non-coding transcriptome as a dynamic regulator of cancer metastasis. Cancer and Metastasis Reviews, 33(1), 1–16.

26. Decaestecker, E., De Meester, L., Ebert, D. (2002). In deep trouble: Habitat selection constrained by multiple enemies in zooplankton. Proceedings of the National Academy of Sciences of the United States of America, 99(8), 5481-85.

27. Decaestecker, E., De Meester, L., Mergeay, J. (2009). Cyclical parthenogenesis in Daphnia: Sexual versus asexual reproduction. In: Van Dijk P., Maertens K., Schoen I. (Eds.), Lost sex: the evolutionary biology of parthenogenesis. Dordrecht: Springer Netherlands, 295-316.

28. Decaestecker, E., Labbé, P., Ellegaard, K., Allen, J., Little, T. (2011). Candidate immune gene expression in the ecological genetics model Daphnia. Developmental and Comparative Immunology, 35(10), 1068-77.

29. Dekervel, J., Bulle, A. S., Windmolders, P., Lambrechts, D., Van Cutsem, E., Verslype, C., van Pelt, J. (2017). Acriflavine Inhibits Acquired Drug Resistance by Blocking the Epithelial-to-Mesenchymal Transition and the Unfolded Protein Response. Translational Oncology, 10(1),59-69.

30. de Martel, C., Ferlay, J., Franceschi, S., Vignat, J., Bray, F., Forman, D., Plummer, M. (2012). Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncology, 13(6), 607-15.

31. Deplancke, B., Gaskins, H.R. (2003). Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J, 17, 1310–12.

32. Diaz, R.J., Rosenberg, R. (1995). Marine benthic hypoxia: A review of its ecological effects and the behavioural responses of benthic macrofauna. Oceanography and Marine Biology, 33, 245–303.

33. Diaz Heijtz, R., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibber, M. L., Forssberg, B. E., Pettersson, S. (2011). Normal gut microbiota modulates brain development and behavior. PNAS, 108(7), 3047–52.

34. Díaz-López, A., Moreno-Bueno, G., Cano, A. (2014). Role of microRNA in epithelial to mesenchymal transition and metastasis and clinical perspectives. Cancer Management and Research, 6, 205–16.

35. Diepenbruck, M., Christofori, G. (2016). Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? Current Opinion in Cell Biology, 43, 7–13.

36. Dillon, R. J., Vennard, C.T., Buckling, A., Charnley, A.K. (2005). Diversity of locust gut bacteria protects against pathogen invasion. Ecology Letters, 8, 1291-98.

37. Du, W., Liu, X., Fan, G., Zhao, X., Sun, Y., Wang, T., Zhao, R., Wang, G., Zhao, C., et al. (2014). From cell membrane to the nucleus: An emerging role of E-cadherin in gene transcriptional regulation. Journal of Cellular and Molecular Medicine, 18(9), 1712–19.

38. Dziga, D., Wasylewski, M., Wladyka, B., Nybom, S., Meriluoto, J. (2013). Microbial Degradation of Microcystins. Chemical research in Toxicology, 26, 841-52.

39. Dzutsev, A., Goldszmid, R.S., Viaud, S., Zitvogel, L., Trinchieri, G. (2015) The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. European Journal of Immunology, 45, 17–31.

40. Ebert, D. (2005). Ecology, Epidemiology, and Evolution of Parasitism in Daphnia. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books

41. Ebos, J. M. L., Lee, C. R., Kerbel, R. S. (2009). Tumor and Host-Mediated Pathways of Resistance and Disease Progression in Response to Antiangiogenic Therapy. Clinical Cancer Research, 15(16), 5020-25.

42. Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornnell, H. H., Ibrahim-Hashim, A., Bailey, K., Balagurunathan, Y., Rothberg, J. M., Sloane, B. F., et al. (2013). Acidity generated by the tumor microenvironment drives local invasion. Cancer Research, 73(5), 1524–35.

43. Fabbri, M., Paone, A., Calore, F., Galli, R., Gaudio, E., Santhanam, R., Lovat, F., Fadda, P., Mao, C., Nuovo, G. J., et al. (2012). MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. PNAS, 109(31), E2110-6.

44. Fischer, K. R., Durrans, A., Lee, S., Sheng, J., Li, F., Wong, S. T. C., Choi, H., El Rayes, T., Ryu, S., Troeger, J., et al. (2015). Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature, 527, 472-88.

45. Fox, H. M. (1948) The Haemoglobin of Daphnia. The Royal Society, 135(879).

46. Freese, H. M., Schink, B. (2011). Composition and stability of the microbial community inside the digestive tract of the aquatic crustacean Daphnia magna. Microbial Ecology, 62(4), 882–94.

47. Friedrich, D., Fecher, A.R., Rupp, J., Deepe, G.S.J. (2017). Impact of HIF-1αand hypoxia on fungal growth characteristics and fungal immunity. Microbes and Infection, 19(3), 204-9.

48. Furuta, G.T., Turner, J.R., Taylor, C.T., Hershberg, R.M., Comerford, K., Narravula, S., Podolsky, D.K., Colgan, S.P. (2001). Hypoxia-inducible Factor 1–dependent Induction of Intestinal Trefoil Factor Protects Barrier Function during Hypoxia. Journal of Experimental Medicine, 193 (9), 1027–34.

49. Garrett, W. S. (2015). Cancer and the Microbiota. Science, 348 (6230), 80-86.

50. Gatesoupe, F.-J., Huelvan, C., Le Bayon, N., Le Delliou, H., Madec, L., Mouchel, O, et al. (2016) The highly variable microbiota associated to intestinal mucosa correlates with growth and hypoxia resistance of sea bass, Dicentrarchus labrax, submitted to different nutritional histories. BMC Microbiology, 16(266), 1-13.

51. Gehringer, M. M., Shephard, E. G., Downing, T. G., Wiegand, C., Neilan, B. A. (2004). An investigation into the detoxification of microcystin-LR by the glutathione pathway in Balb/c mice. International Journal of Biochemistry and Cell Biology, 36(5), 931-41.

52. Geva-Zatorsky, N., Alvarez, D., Hudak, J.E., Reading, N.C., Erturk-Hasdemir, D., Dasgupta, S., et al. (2015). In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria. Nature Medicine, 21(9), 1091-100.

53. Gilkes, D. M., Semenza, G., L. (2013). Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncology, 9(11), 1623–1636.

54. Gjorevski, N., Boghaert, E., Nelson, C. M. (2012). Regulation of epithelial-mesenchymal transition by transmission of mechanical stress through epithelial tissues. Cancer Microenvironment, 5(1), 29–38.

55. Gonçalves, A.M.M., Castro, B.B., Pardal, M.A., Gonçalves, F. (2007). Salinity effects on survival and life history of two freshwater cladocerans (Daphnia magna and Daphnia longispina). International Journal of LimnologyI, 43(1), 13-20.

56. Gorr, T. A. (2004). Daphnia and Drosophila: two invertebrate models for O2 responsive and HIF-mediated regulation of genes and genomes. International Congress Series, 1275, 55–62.

57. Gonzalez, C. (2013) Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nature Reviews Cancer,13(3),172-83.

58. Gros, J., Tabin, C. J. (2014). Vertebrate Limb Bud Formation Is Initiated by Localized Epithelial-to-Mesenchymal Transition. Science, 343(6176), 1253-56.

59. Hanahan, D., Weinberg, R. a. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–74.

60. Harris, T. J. C., Tepass, U. (2010) Adherens junctions: from molecules to morphogenesis. Nature reviews: Molecular Cell Biology, 11, 502-14.

61. Heckmann, L.- H., Sibly, R. M., Connon, R., Hooper, H. L., Hutchinson, T. H., Maund, S. J., Hill, C. J., Bouetard, A., Callaghan, A. (2008). Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna. Genome Biology, 9(R40), R40.

62. Herrero, A., Muro-Pastor, A. M., Flores, E. (2001). Nitrogen Control in Cyanobacteria. Journal of Bacteriology, 183(2), 411–25.

63. Homer, D. H., Waller, W. (1983). Chronic effect of reduced dissolved oxygen on Daphnia magna. Water Air Soil Pollution, 20(1), 23-8.

64. Hudnell, H. K. (2010). The state of U.S. freshwater harmful algal blooms assessments, policy and legislation. Toxicon, 55(5), 1024–1034.

65. Hwang, W.-L., Jiang, J.-K., Yang, S.-H., Huang, T.-S., Lan, H.-Y., Teng, H.-W., et al. (2014). MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nature Cell Biology, 16(3), 268–80.

66. Imai, T., Horiuchi, A., Wang, C., Oka, K., Ohira, S., Nikaido, T., Konishi, I. (2003). Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. The American Journal of Pathology, 163(4), 1437–47.

67. Imamichi ,Y., Menke, A. (2007). Signaling pathways involved in collagen-induced disruption of the E-cadherin complex during epithelialmesenchymal transition. Cells Tissues Organs, 185, 180-90.

68. Irrazábal, T., Belcheva, A., Girardin, S.E., Martin, A., Philpott, D.J. (2014). The Multifaceted Role of the intestinal Microbiota in Colon Cancer. Molecular Cell, 54, 309-20.

69. Jiang, J., Tang, Y. L., Liang, X. H. (2011). EMT: A new vision of hypoxia promoting cancer progression. Cancer Biology and Therapy, 11(8), 714–23.

70. Johnston, D. S., Ahringer, J. (2010). Cell Polarity in Eggs and Epithelia: Parallels and Diversity. Cell, 141(5), 757-74.

71. Kalluri, R., Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 119(6), 1420-28.

72. Kelly, C.J., Zheng, L., Campbell, E.L., Saeedi, B., Scholz, C.C., Bayless, A.J., et al. (2015). Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell Host & Microbe, 17, 662–67.

73. Kirienko, N. V., Mani, K., Fay, D. S. (2010). Cancer models in Caenorhabditis elegans. Developmental Dynamics, 239(5), 1413–48.

74. Klüttgen, B., Dulmer, U., Engels, M., Ratre, H. T. (1994). ADaM , An Artificial Freshwater for the Culture of Zooplankton. Water Research, 28(3), 743–46.

75. Kohl, K. D., Weiss, R. B., Cox, J., Dale, C., Dearing, M. D. (2014). Gut microbes of mammalian herbivores facilitate intake of plant toxins. Ecol. Lett., 17, 1238-46.

76. Kokkinos, M. I., Murthi, P., Wafai, R., Thompson, E. W., Newgreen, D. F. (2010). Cadherins in the human placenta--epithelial-mesenchymal transition (EMT) and placental development. Placenta, 31(9), 747–55.

77. Komarova, Y. A., Mehta, D., Malik, A. B. (2007). Dual regulation of endothelial junctional permeability. Science Signaling, 412, re8.

78. Kozich, J.J., Westcott, S.L., Baxter, N.T., Highlander, S.K., Schloss, P.D. (2013). Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the Miseq Illumina Sequencing Platform. Applied and Environmental Microbiology, 79, 5112–20.

79. Kume, K., Haraguchi, M., Hijioka, H., Ishida, T., Miyawaki, A., Nakamura, N., Ozawa, M. (2013). The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells. Biochemical and Biophysical Research Communications, 430(3), 889–94.

80. Kump, L. R., Junium, C., Arthur, M. a., Brasier, A., Fallick, A. E., Melezhik, V., Lepland, A., Čne, A. E., Luo, G. (2011). Isotopic evidence for massive oxidation of organic matter following the great oxidation event. Science, 334(December), 1694–96.

81. Lai, K.-P., Li, J.-W., Chan, C. Y.-S., Chan, T.-F., Yuen, K. W.-Y., Chiu, J. M.-Y. (2016). Transcriptomic alterations in Daphnia magna embryos from mothers exposed to hypoxia. Aquatic Toxicology (Amsterdam, Netherlands), 177, 454–63.

82. Lamkemeyer, T., Zeis, B., Decker, H., Jaenicke, E., Waschbüsch, D., Gebauer, W., Markl, J., Meissner, U., Rousselot, M., Zal, F., et al. (2006). Molecular mass of macromolecules and subunits and the quaternary structure of hemoglobin from the microcrustacean Daphnia magna. FEBS Journal, 273(14), 3393–10.

83. Lamouille, S., Xu, J., Derynck, R. (2014). Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews. Molecular Cell Biology, 15(3), 178–96.

84. Leopold, P. L., Vincent, J., Wang, H. (2012). A comparison of epithelial-to-mesenchymal transition and re-epithelialization. Seminars in Cancer Biology, 22(5–6), 471–83.

85. Li, Q., Sodroski, C., Lowey, B., Schweitzer, C. J., Cha, H., Zhang, F., Liang, T. J. (2016). Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America, 113(27), 7620–5.

86. Lin, F., Wang, N., Zhang, T.-C. (2012). The role of endothelial-mesenchymal transition in development and pathological process. IUBMB Life, 64(9), 717–23.

87. Little, T. J., O'Connor, B., Colegrave, N., Watt, K., Read, A. F. (2003). Maternal transfer of strain-specific immunity in an invertebrate. Current Biology, 13, 489–92.

88. Lozupone, C., Knight, R. (2005). UniFrac: a New Phylogenetic Method for Comparing Microbial Communities. Applied and Environmental Microbiology, 71(12), 8228–35.

89. Lundgren, K., Nordenskjöld, B., Landberg, G. (2009). Hypoxia, Snail and incomplete epithelial-mesenchymal transition. British Journal of Cancer, 101, 1769-81.

90. Leatherman, J. L., DiNardo, S. (2008). Zfh-1 Controls Somatic Stem Cell Self-Renewal in the Drosophila Testis and Nonautonomously Influences Germline Stem Cell Self-Renewal. Cell Stem Cell, 3(1), 44–54.

91. Macke, E., Callens, M., De Meester, L., Muylaert, K., Decaestecker, E. (in revision) Microbiome-mediated adaptation to climate change: how gut microbes drive resistance to toxic algal blooms.

92. Mani, S. a, Guo, W., Liao, M., Eaton, E. N., Ayyanan, A., Zhou, Y., Brooks, M., Reinhard, F., Zhang, C. C., Shipitsin, M., et al. (2009). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–15.

93. Manzanares, M., Locascio, A., Nieto, M. A. (2001). The increasing complexity of the Snail gene superfamily in metazoan evolution. TRENDS in Genetics, 17(4), 178–81.

94. Marcucci, F., Bellone, M., Caserta, C. A., Corti, A. (2014). Pushing tumor cells towards a malignant phenotype: Stimuli from the microenvironment, intercellular communications and alternative roads. International Journal of Cancer, 135(6), 1265-76.

95. Metchnikoff, E., 1893. Lectures on the Comparative Pathology of Inflammation. (Translated from the French by F.A. and E.H. Starling) Kegan Paul, Trench Trubner and Co., Ltd., London.

96. Metzen, E., Stiehl, D.P., Doege, K., Marxsen, J.H., Hellwig-Bürgel, T., Jelkmann, W. (2005). Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia responsive element. The Biochemical Journal, 387(3), 711-17.

97. Mimeault, M., Batra, S. K. (2013). Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells. Journal of Cellular and Molecular Medicine, 17(1), 30–54.

98. Miner, B. E., De Meester, L., Pfrender, M. E., Lampert, W., Hiarston, N. G. (2012). Linking genes to communities and ecosystems: Daphnia as an ecogenomic model. Proceedings of the Royal Society B: Biological Sciences, 279(1735), 1873-82.

99. Moreno-Indias, I., Torres, M., Montserrat, J. M., Sanchez-Alcoholado, L., Cardona, F., Tinahones, F. J., Gozal, D., Poroyko, V. A., Navajas, D., Queipo-Ortuño, M. I., et al. (2015). Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. The European respiratory journal, 45(4), 1055-65.

100. Nakajima, Y., Yamagishi, T., Hokari, S., Nakamura, H. (2000). Mechanisms Involved in Valvuloseptal Endocardial Cushion Formation in Early Cardiogenesis: Roles of Transforming Growth Factor (TGF)-b and Bone Morphogenetic Protein (BMP). The Anatomical Record , 258(2), 119–27.

101. Narumiya, S., Tanji, M., Ishizaki, T. (2009). Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev , 28(1), 65–76.

102. Natzle, J. E., Kiger, J. A., Green, M. M. (2008). Bursicon signaling mutations separate the epithelial-mesenchymal transition from programmed cell death during Drosophila melanogaster wing maturation. Genetics, 180(2), 885–93.

103. Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., Pettersson, S. (2012). Host-gut microbiota metabolic interactions. Science, 336(6086), 1262–7.

104. Nieto, M. A., Huang, R. Y.-J., Jackson, R. a., Thiery, J. P. (2016). EMT: 2016. Cell, 166(1), 21–45.

105. Nistico, P., Bissell, M. J., Radisky, D. C. (2009). Epithelial-Mesenchymal Transition: General Principles and Pathological Relevance with Special Emphasis on the Role of Matrix Metalloproteinases. Cold Spring Harbor Perspectives in Biology, 4(2), a011908.

106. Ohkubo, T., Ozawa, M. (2004). The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation. Journal of Cell Science, 117(9), 1675–85.

107. Ozdemir, A., Fisher-Aylor, K. I., Pepke, S., Samanta, M., Dunipace, L., Mccue, K., Zeng, L., Ogawa, N., Wold, B. J., Stathopoulos, A. (2011). High resolution mapping of Twist to DNA in Drosophila embryos : Efficient functional analysis and evolutionary conservation. Genome research, 21, 566–77.

108. Parrella, A., Kundi, M., Lavorgna, M., Criscuolo, E., Russo, C., Isidori, M. (2014). Toxicity of exposure to binary mixtures of four anti-neoplastic drugs in Daphnia magna and Ceriodaphnia dubia. Aquatic Toxicology, 157, 41–6.

109. Peerakietkhajorn, S., Kato, Y., Kasalický, V., Matsuura, T., Watanabe, H. (2016). Betaproteobacteria Limnohabitans strains increase fecundity in the crustacean Daphnia magna: symbiotic relationship between major bacterioplankton and zooplankton in freshwater ecosystem. Environmental Microbiology, 18(8), 2366–74.

110. Peinado, H., Olmeda, D., Cano, A. (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Reviews. Cancer, 7(6), 415–28.

111. Pilli, V. S., Gupta, K., Kotha, B. P., Aradhyam, G. K. (2015). Snail-mediated Cripto-1 repression regulates the cell cycle and epithelial-mesenchymal transition-related gene expression. FEBS Letters, 589(11), 1249–56.

112. Porat, R. A. M., Teltsch, B., Perelman, A., Dubinsky, Z. V. Y. (2001). Diel buoyancy changes by the cyanobacterium Aphanizomenon ovalisporum from a shallow reservoir. Journal of Plankton Research, 23(7), 753-63.

113. Prabhakar, N. R., Semenza, G. L. (2012). Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiological Reviews, 92(3), 967–1003.

114. Qi, W., Nong, G., Preston, J. F., Ben-Ami, F., Ebert, D. (2009). Comparative metagenomics of Daphnia symbionts. BMC Genomics, 10, 172.

115. Qian, X., Anzovino, A., Kim, S., Suyama, K., Yao, J., Hulit, J., Agiostratidou, G., Chandiramani, N., McDaid, H. M., Nagi, C., et al. (2014). N-cadherin/FGFR promotes metastasis through epithelial-tomesenchymal transition and stem/progenitor cell-like properties. Oncogene, 33, 3411–21.

116. Recamier JC. (1829). Recherches sur le traitement du cancer sur la compression methodique simple ou combinee et sur l'histoire generale de la meme maladie. 2nd ed.

117. Ren, Y., Yang, M., Chen, M., Zhu, Q., Zhou, L., Qin, W., Wang, T. (2017). Microcystin-LR promotes epithelial-mesenchymal transition in colorectal cancer cells through PI3-K/AKT and SMAD2. Toxicology Letters, 265, 53-60.

118. Ridley, A. J. (2011). Life at the Leading Edge. Cell, 145(7), 1012-22.

119. Lionel Rigottier-Gois, L. (2013). Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis. The ISME Journal, 7(7), 1256-61.

120. Rogers, C. D., Saxena, A., Bronner, M. E. (2013) Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT. J. Cell Biol., 203(5), 835–47.

121. Rossignol, F., Vache, C., Clottes, E. (2002). Natural antisense transcripts of hypoxia-inducible factor 1alpha are detected in different normal and tumour human tissues. Gene, 299, 135-40.

122. Routtu, J., Hall, M.D., Albere, B., Beisel, C., Bergeron, R.D., Chaturvedi, A., Choi, J.-H., Colbourne, J., De Meester, L., Stephens, M.T., et al. (2014). An SNP-based second-generation genetic map of Daphnia magna and its application to QTL analysis of phenotypic traits. BMC Genomics, 15(1033).

123. Rowe, R. G., Lin, Y., Shimizu-Hirota, R., Hanada, S., Neilson, E. G., Greenson, J. K., Weiss, S. J. (2011). Hepatocyte-Derived Snail1 Propagates Liver Fibrosis Progression. Molecular and Cellular Biology, 31(12), 2392–2403.

124. Rubinstein, M. R., Wang, X., Liu, W., Hao, Y., Cai, G., Han, Y. W. (2013). Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe, 14, 195–206.

125. Said, N. A. B. M., Williams, E. D. (2011). Growth factors in induction of epithelial-mesenchymal transition and metastasis. Cells, Tissues, Organs, 193(1–2), 85–97.

126. Sarnelle, O., Gustafsson, S., Hansson, L.-A. (2010). Effects of cyanobacteria on fitness components of the herbivore Daphnia. Journal of Plankton Research, 32(4), 471-77.

127. Sauka-Spengler, T., Bronner-Fraser, M. (2008). A gene regulatory network orchestrates neural crest formation. Nature Reviews Molecular Cell Biology, 9(7), 557-68.

128. Semenza, G. L. (2012). Hypoxia-Inducible Factors in Physiology and Medicine. Cell, 148(3), 399-408.

129. Semenza, G. L. (2014). Oxygen Sensing, Homeostasis, and Disease. New England Journal of Medicine, 365(6), 537–47.

130. Sethi, N., Kang, Y. (2011). Unravelling the complexity of metastasis - molecular understanding and targeted therapies. Nature Reviews Cancer, 11(10), 735–48.

131. Shaw, T. J., Martin, P. (2016). Wound repair: a showcase for cell plasticity and migration. Current Opinion in Cell Biology, 42, 29–37.

132. Sison-Mangus, M. P., Mushegian, A. a, Ebert, D. (2014). Water fleas require microbiota for survival, growth and reproduction. ISME, 9(1), 1–9.

133. Smallhorn, M., Murray, M.J., Saint, R. (2004). The epithelial-mesenchymal transition of the Drosophila mesoderm requires the Rho GTP exchange factor Pebble. Development, 131(11), 2641-51.

134. Smirnov, N.N. (2017). Physiology of the Cladocera, Second Edition. Elsevier Inc., UK, 401p. ISBN:978-0-12-805194-8.

135. Stefanatos R. K. A., Vidal, M. (2011) Tumor invasion and metastasis in Drosophila: A bold past, a bright future. Journal of Genetics and Genomics, 38(10), 431-38.

136. Steinestel, K., Eder, S., Schrader, A.J., Steinestel, J. (2014). Clinical significance of epithelial-mesenchymal transition. Clinical and Translational Medicine, 3(17), 1-12.

137. Takahashi, S., Piao, W., Matsumura, Y., Komatsu, T., Ueno, T. Takuya T., Kamachi, T., Kohno, M., Nagano, T., Hanaoka, K. (2012). Reversible off-on fluorescence probe for hypoxia and imaging of hypoxia-normoxia cycles in live cells. Journal of the American Chemical Society,134(48), 19588-91.

138. Talmadge, J. E., Fidler, I. J. (2010). AACR centennial series: The biology of cancer metastasis: Historical perspective. Cancer Research, 70(14), 5649–69.

139. Tam, W. L., Weinberg, R. A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nature Medicine, 19(11), 1438–49.

140. Tarin, D. (2005). The Fallacy of Epithelial Mesenchymal Transition in Neoplasia. Cancer research, 65(14), 5996–6001.

141. Tasiemski, A., Massol, F., Cuvillier-Hot, V., Boidin-Wichlacz, C., Roger, E., Rodet, F., Fournier, I., Thomas, F., Salzet, M. (2015). Reciprocal immune benefit based on complementary production of antibiotics by the leech Hirudo verbana and its gut symbiont Aeromonas veronii. Scientific Reports, 5(1), 17498.

142. Terova, G., Rimoldi, S., Corà, S., Bernardini, G., Gornati, R., Saroglia, M. (2008). Acute and chronic hypoxia affects HIF-1αmRNA levels in sea bass (Dicentrarchus labrax). Aquaculture, 279(1), 150–9.

143. Thiery, J. P., Acloque, H., Huang, R. Y. J., Nieto, M. A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871–90.

144. Tiwari, N., Gheldof, A., Tatari, M., Christofori, G. (2012). EMT as the ultimate survival mechanism of cancer cells. Seminars in Cancer Biology, 22(3), 194–207.

145. Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., Clerici, C. (2004). Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1αand HIF-2αExpression in Lung Epithelial Cells. Journal of Biological Chemistry, 279(15), 14871-8.

146. Uchida, H., Maruyama, T., Nishikawa-Uchida, S., Oda, H., Miyazaki, K., Yamasaki, A., Yoshimura, Y. (2012). Studies using an in vitro model show evidence of involvement of epithelial-mesenchymal transition of human endometrial epithelial cells in human embryo implantation. The Journal of Biological Chemistry, 287(7), 4441–50.

147. Wächtler, B., Citiulo, F., Jablonowski, N., Förster, S., Dalle, F., Schaller, M., Wilson, D., Hube, B. (2012). Candida albicans-Epithelial Interactions: Dissecting the Roles of Active Penetration, Induced Endocytosis and Host Factors on the Infection Process. PLoS ONE, 7(5), e36952.

148. Wang, P.-J., Chien, M.-S., Wu, F.-J., Chou, H.-N., Lee, S.-J. (2005). Inhibition of embryonic development by microcystin-LR in zebrafish, Danio rerio. Toxicon : Official Journal of the International Society on Toxinology, 45(3), 303–8.

149. Wang, P., Zhao, J., Corsi, A. K. (2006). Identification of novel target genes of CeTwist and CeE/DA. Developmental Biology, 293(2), 486–98.

150. Wang, C., Gu, S., Yin, X., Yuan, M., Xiang, Z., Li, Z., Cao, H., Meng, X., Hu, K., Han, X. (2016). The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells. Toxicon : Official Journal of the International Society on Toxinology, 115, 81–8.

151. Warzecha, C. C., Carstens, R. P. (2012). Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT). Seminars in Cancer Biology, 22(5-6), 417–27.

152. Wei, L., Hoole, D., Sun, B. (2014). Identification of apoptosis-related genes and transcription variations in response to microcystin-LR in zebrafish liver. Toxicology and Industrial Health, 30(9), 777–84.

153. Wilhelm, S., Gary R. LeCleir, G. R., Bullerjahn, G. S., McKay, R. M., Saxton, M. A., Twiss, M. R., Bourbonniere, R. A. (2014). Seasonal changes in microbial community structure and activity imply winter production is linked to summer hypoxia in a large lake. FEMS Microbiology Ecology, 87(2), 475-85.

154. Vega, S., Morales, A. V, Ocaña, O. H., Valdés, F., Fabregat, I., Nieto, M. A. (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes & Development,18(10), 1131–43.

155. Xu, J., Lamouille, S., Derynck, R. (2009). TGF-beta-induced epithelial to mesenchymal transition. Cell Research, 19(2), 156–72.

156. Yang, M.-H., Wu, M.-Z., Chiou, S.-H.; Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., Wu, K.-J. (2008). Direct regulation of TWIST by HIF-1αpromotes metastasis. Nature Cell Biology, 10(3), 295-305.

157. Yang, Q., Li, Z., Cao, J., Zhang, S., Zhang, H., Wu, X., Zhang, Q., Liu, X.,Söderhäll, K. (2014). Selection and Assessment of Reference Genes for Quantitative PCR Normalization in Migratory Locust Locusta migratoria (Orthoptera: Acrididae). PLoS ONE, 9(6), e98164.

158. Zhang, K., Rodriguez-Aznar, E., Yabuta, N., Owen, R. J., Mingot, J. M., Nojima, H., Nieto, M. A., Longmore, G. D. (2012). Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. The EMBO Journal, 31(1), 29–43.

159. Zhou, B. P., Deng, J., Xia, W., Xu, J., Li, Y. M., Gunduz, M., Hung, M.-C. (2004). Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nature Cell Biology, 6(10), 931–40.

160. Zhou, Z., Wang, S., Song, C., Hu, Z. (2016). Paeoniflorin prevents hypoxia-induced epithelial -mesenchymal transition in human breast cancer cells. OncoTargets and therapy, 9, 2511-18.

 

Universiteit of Hogeschool
Biologie
Publicatiejaar
2017
Promotor(en)
Ellen Decaestecker
Kernwoorden
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