A new study has suggested that normal cells in tumors can trigger the growth of tumor cells after losing a vital tumor suppressor gene.
Led by researchers at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), the study examined what happens when normal cells called fibroblasts in mouse mammary tumours lose an important tumour-suppressor gene called Pten (pronounced "P-ten").
AdvertisementThe findings suggested new strategies for controlling tumour growth by developing drugs that disrupt the communication between tumour cells and the normal cells within the tumour.
They also provided insight into the mechanisms that control the co-evolution of cancer cells and surrounding normal cells in tumours, and demonstrated how the Pten gene normally suppresses cancer development, the researchers say.
"Our study is the first to define a specific pathway in tumor fibroblasts that reprograms gene activity and the behaviour of multiple cell types in the tumor microenvironment, including tumor cells themselves," said co-principal investigator Dr. Michael Ostrowski, professor and chair of molecular and cellular biochemistry.
"Along with increasing basic knowledge about how tumors grow and spread, these findings have direct translational implications for the treatment of breast-cancer patients."
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 tumour 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 tumour and throughout the mammary gland.
"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," said co-principal investigator Gustavo Leone
Ostrowski, Leone and their colleagues began this study by examining human invasive breast tumours from 126 patients for microRNA changes after PTEN loss.
The study has been published in the journal Nature Cell Biology.