Migration of the zebrafish lateral line as a model for metastasis

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NHGRI	CANCER-9

* FARE Award Winner

Authors

• V.E. Gallardo
• G. Varshney
• M.L. Allende
• S.M. Burgess

Abstract

The migrating primordium of the zebrafish posterior lateral line (PLLp) has emerged as a powerful model to investigate the molecular mechanisms of cell migration and cancer metastasis. The PLL is a mechanosensory system that detects water movements. Its individual organs, the neuromasts, are formed by regular deposition from a group of migrating cells that travel along the body of the fish. The collective migration of the primordium cells has been the focus of intense study due to the parallels of this cellular behavior with that of invasive cancer cells. Through the combination of transgenic fish, FACS and microarray analysis we identified a repertoire of key genes expressed in the primordium. Interestingly, mostly of the genes captured in this study have demonstrated roles in collective cell migration and cancer progression. Given the cellular and molecular equivalences between both processes, we carried out a HTS to identify drug candidates that inhibit the invasive/metastatic phenotype. Using the PLLp as a readout for migratory inhibition, we identified 66 compounds interfering with primordium migration. Finally, we envision that the use of HTS to identify drugs that inhibit cancer progression using zebrafish, may be crucial to create efficient targeted therapies to treat human cancers.

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