Researchers study zebrafish embryo skin to find link between low calcium and colon cancer

Published on December 14, 2013 at 8:30 AM · No Comments

A tiny, transparent fish embryo and a string of surprises led scientists to a deeper understanding of the perplexing link between low calcium and colon cancer.

By studying zebrafish embryo skin, University of Michigan researchers decoded cell messages underlying abnormal colonic cell growth of the kind that can lead to tumors and colon cancer in calcium deficient individuals. They have also tested this new mechanism in human colon cancer cells.

Ultimately, the new biological mechanism unraveled in zebrafish will help scientists understand the pathways that fuel low calcium-related abnormal colonic cell growth and how to stop that growth, said Cunming Duan, professor in the U-M Department of Molecular, Cellular & Developmental Biology.

To do this, Duan and colleagues used a fluorescent protein to mark a type of epithelial cell, whose job it is to import calcium into the body. The cells behave essentially the same in people and zebrafish, but scientists can study the live cells in zebrafish embryos because they sit on the skin, instead of in the intestine and gut, as with humans.

When the researchers placed the zebrafish embryos in calcium-depleted water, they were surprised that it activated a particular growth factor that stimulates division and growth in these epithelial cells. The calcium transporter (TRPV5/6) must be present for this activation, which is an apparent survival mechanism for animals to import calcium into cells in low-calcium environments.

Animals and people cannot survive without enough calcium, so regulating calcium is critical, Duan said. The link of a calcium transporter to this growth factor signaling pathway is new, and scientists demonstrated the same pathway at work in human colon cancer cells. The discovery also demonstrates the built-in, evolutionarily conserved calcium regulation mechanism that helps humans and animals survive low-calcium conditions.

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