Fish Embryo Helps Reveal Link Between Colon Cancer and Calcium Deficiency

A transparent fish embryo helped scientists better understand how low calcium levels were linked to colon cancer

A transparent fish embryo helped scientists better understand how low calcium levels were linked to 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.

Viable New Therapeutic Path For Colon Cancer Treatment Discovered While Targeting Stem Cells
A promising new approach to treating colorectal cancer was discovered by scientists and surgeons at Princess Margaret Cancer Centre.

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.

Key Link Responsible for Colon Cancer Initiation and Metastasis discovered
CXCR2 - a key genetic culprit that is implicated in the tumor formation, growth and progression in a mouse model of colon cancer has been identified by scientists.

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.

Understanding the mechanisms behind the calcium-induced abnormal colonic cell growth is the first step in developing drugs or other therapies to prevent it, Duan said.

Current National Screening Guidelines may Miss 10 Percent of Colon Cancers
When current national screening guidelines are followed for people with a family history of adenomas (colon polyps that lead to colon cancer), up to 10 percent of colorectal cancers could be missed.

"Theoretically, it's a possibility you could someday apply this to humans and block human colon cancer cell division," he said.

Duan said several surprising findings and unlikely players converged to push the research along. First, Duan's lab doesn't even study cancer, but rather the growth factor in zebrafish embryo development.

"We found accidentally that these cells divide like crazy when you change the water calcium level," Duan said.

After that, the research swerved in a new direction.

"We then wondered if the growth factor involved had anything to do with colon cancer," he said.

Source-Eurekalert