Cellular Collaboration

Study Shows How Normal Cells Fuel Tumor Growth  

Leone_OstrowskiResearchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) have discovered how normal cells within tumors can fuel tumor growth.

Their study examined what happens when normal cells called fibroblasts in mouse mammary tumors lose the Pten tumor-suppressor gene. The findings:

  • Suggest new strategies for controlling tumor growth by developing drugs that disrupt communication between tumor cells and normal cells;
  • Provide insight into mechanisms that control the co-evolution of cancer cells and surrounding normal cells in tumors;
  • Demonstrate how the Pten gene normally suppresses cancer development.

“Our study is the first to define a specific pathway in tumor fibroblasts that reprograms gene activity and the behavior of multiple cell types in the tumor microenvironment, including tumor cells themselves,” says co-principal investigator Michael Ostrowski, PhD, co-leader of the Molecular Biology and Cancer Genetics Program at the OSUCCC – James.

The findings increase basic knowledge about how tumors grow and spread, and they have translational implications for the treatment of breast-cancer patients, Ostrowski says.

The researchers found that Pten regulates a molecule called microRNA-320 (miR-320), and that 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 rise in the fibroblast, activating genes that cause the fibroblast to secrete more than 50 factors that stimulate proliferation and invasiveness of nearby cancer cells.

“The cancer field has long focused solely on targeting tumor cells for therapy,” says co-principal investigator Gustavo Leone, PhD, associate director for basic research at the OSUCCC – James. “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.”

Published in the journal Nature Cell Biology.

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