Researchers discover how normal cells in tumors can drive cancer growth
June 25, 2017
"Along with increasing basic knowledge about how tumors grow and spread, these findings have direct translational implications for the treatment of breast-cancer patients," says Ostrowski, who is a member of the OSUCCC - James Molecular Biology and Cancer Genetics program.
The researchers found that Pten regulates a molecule called microRNA-320 (miR-320), and that the loss of Pten leads to a dramatic drop in levels of that molecule in a tumor fibroblast. With little miR-320 around, levels of a protein called ETS2 (pronounced Ets-two) rise in the fibroblast.
Finally, the abundance of ETS2 activates a number of genes that cause the fibroblast to secrete more than 50 factors that stimulate the proliferation and invasiveness of nearby cancer cells. It also causes the reprogramming of other fibroblasts in the tumor and throughout the mammary gland.
"The cancer field has long focused solely on targeting tumor cells for therapy," says co-principal investigator Gustavo Leone, associate professor of molecular virology, immunology and medical genetics. "Our work suggests that modulation of a few key molecules such as miR-320 in noncancer cells in the tumor microenvironment might be sufficient to impede the most malignant properties of tumor cells."
Ostrowski, Leone and their colleagues began this study by examining human invasive breast tumors from 126 patients for microRNA changes after PTEN loss.
Key technical findings include the following: