Molecular changes in tissue microenvironment may promote colorectal cancer

Our goal is to study this epithelial 'soil' in which cells, transformed into cancer-causing 'weeds,' can arise and proliferate, says Tatianna Larman, M.D., assistant professor of pathology at the Johns Hopkins University School of Medicine. "Finding what conditions in the epithelial stem cell niche [microenvironment] promote neoplasia [abnormal cell growth] and the acquisition of cancer driver mutations [changes in genetic sequences that cause cells to become cancerous] may help us identify ways to 'clean the garden' before cancer can emerge."
In a study published in the May 2021 issue of the journal Neoplasia, Larman and her colleagues used normal colon intestinal organoids—cell lines grown from intestinal stem cells that function like miniature colons—to see if changing the microenvironment alone would lead to epithelial changes that are precursors to cancer.
We know from research studies that intestinal stem cells require certain 'niche factors' to maintain normal growth and function—a balance known as homeostasis— and that precursors to cancer can grow without these factors, says Larman. When we removed one of those niche factors, a protein known as epidermal growth factor [EGF], most organoids died as expected. However, over many months, the rare survivors surprisingly adapted to growth without EGF and exhibited many features of neoplasia, such as abnormal morphology and chromosome numbers."
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John
Editorial Assistant
Immunogenetics Open Access