0402 GMT January 23, 2019
Deadly tumor-initiating cells seed metastases throughout the body and cause relapses in patients. Whether these tumor-initiating cells can also be referred to as stem cells, specifically, cancer stem cells, has been up for debate. The question is not purely one of semantics — the label connotes scientists' understanding of those cells' identity and inner workings, Newswise said.
"Our research establishes for the first time the relationship between the normal stem cell program and the cancer stem cell program, albeit in the context of the mammary gland," said Whitehead Institute Founding Member Robert Weinberg. "There may be slight variations on this theme in other epithelial tissues, but at least the relationship is firmly secured in the context of the mammary gland, which seems to be a pretty good model for other epithelial tissues. Tumor-initiating cells are in fact cancer stem cells, but cancer stem cells do not arise from normal stem cells."
In the current line of research, Xin Ye, who is a senior research associate in the Weinberg lab and the lead author, used a mouse model that shows which cells within the normal and cancerous mammary gland express the related master regulators Snail and Slug, both of which confer stem-like traits on mammary cells. Slug, for its part, is especially potent in inducing the mesenchymal cell traits that are associated with high-grade, aggressive carcinomas.
Ye determined that different cell types in distinct tissue layers within the mammary gland express and are influenced by these master regulators. Slug, which regulates gland-reconstituting activity in breast tissue, is expressed at higher levels in normal stem cells found in the basal layer of mammary ducts. Snail, a factor first discovered in the context fruit fly embryonic development, is expressed by tumor-initiating cells in the luminal layer of cells in these ducts. Snail has the power to confer aggressive traits on cancer cells that Slug is incapable of doing when it is expressed at normal levels.