PgmNr Z6006: Investigating Colorectal Cancer Metastasis to Liver in Zebrafish.

Authors:
S. Mukhopadhyay 1 ; M. Mesmar 1 ; J. Gustafsson 1,2 ; C. Williams 2 ; M. Bondesson 1


Institutes
1) University of Houston, Houston, TX; 2) Karolinska Institutet, Solna, Sweden.


Abstract:

Chemokines are known to play a role in cancer. C-C chemokine Receptor type 6 (CCR6) and its sole ligand, CCL20 have been reported to be up-regulated in colorectal cancer (CRC) cells. We are studying the chemotaxis of CCR6-expressing CRC cells to CCL20, whose expression is highest in the liver. It has been suggested that it is due to this chemoattraction that 75% of the CRCs metastasize to the liver. Hence, disruption of the CCR6-CCL20 interaction is one strategy for inhibiting CRC liver metastasis. This hypothesis is being tested using a variety of in vitro assays and in vivo in zebrafish. We investigated CCR6 RNA and protein expression in different CRC cell lines, and selected the highest expressing cell lines for microinjection into zebrafish embryos, following tracking of the fluorescence-labeled migrating cells. When injected to the perivitelline space, SW480 and HT29 cells micro-metastasize to the vasculature. We are now injecting CRC cells into the zebrafish intestine following imaging of cancer cell migration to evaluate whether zebrafish xenografting is a viable model for studies of liver metastasis.