Tumor growth can start from stem cells in the gut, say School of Medicine researchers studying fruit flies.
They found that tumors can grow from adult stem cells that have lost a specific tumor-suppressor gene. The gene, Apc, has previously been implicated in human gastrointestinal cancers, including colon cancer, the second-leading cause of cancer-related death in the Western world.
“A long-standing question in cancer biology is ‘Do tumors arise from specific cell types?'” said lead author Craig A. Micchelli, Ph.D., assistant professor of developmental biology. “We asked what happens when the Apc gene is specifically disabled in fruit fly intestinal stem cells, and we observed that the mutant cells proliferate rapidly to create tumors. Our studies demonstrate that adult stem cells in the intestinal tract of fruit flies can function as a cell of origin for tumorigenesis.”
The study was published in the journal Development.
In the gut of mature fruit flies, a population of stem cells exists to maintain the gut lining. When cells lining the intestinal tract die or are sloughed off, stem cells divide to produce replacements. Normally, just a couple thousand stem cells reside in a fruit fly’s gut and divide as needed to keep the gut healthy.
When the researchers selectively knocked out the Apc gene in these cells, they saw that the cells divided rapidly, forming masses of cells that protruded into the gut interior. These tumor-like masses had characteristics very like those of adenomas of the human gastrointestinal tract. Adenomas are benign tumors that can become malignant.
The Apc gene is often missing in people with the hereditary colon cancer syndrome familial adenomatous polyposis. Without surgery to remove all or part of the colon, colon cancer is virtually inevitable in those with Apc loss.
“The fruit fly now provides a powerful genetic model system that can be used to study the earliest steps of gastrointestinal tumorigenesis,” Micchelli said. “The system can also be used to identify new genes that suppress the rapid proliferation caused by loss of Apc. Such genes constitute novel drug targets capable of retarding tumor growth at a very early stage.”