A team from the Salk Institute reveals two gene-regulating molecules that alter cell signaling within tumor cells to survive and subvert the body's normal immune response. The findings appeared yesterday in Nature Cell Biology.
Normally, cancerous tumors grow so fast that they end up using up all their available blood supply and create a low-oxygen environment called hypoxia. The cells typically tend to self-destruct due to hypoxia, but sometimes in some tumors, the microenvironment surrounding the hypoxic tumor tissue shields it.
"Our findings actually indicate how cancer cells respond to a changing microenvironment and suppress anti-tumor immunity through intrinsic signaling," says Juan Carlos Izpisua Belmonte, Ph.D., senior author of the work. The answer was through microRNAs.
To gain a better understanding, the researchers screened for altered levels of microRNAs and found miR25 and miR93. They then measured the levels of these microRNAs in the tumors of 148 cancer patients and found that tumors with high levels of miR25 and miR93 led to a worse prognosis in patients compared to tumors with lower levels. It was the reverse for another molecule called cGAS. The lower the level of cGAS, in a tumor, the worse the outcome was.
"Given these results, we wondered if these two microRNA molecules, miR25 and miR93, could be lowering cGAS levels to create a protective immunity shield for the tumor," says Min-Zu (Michael) Wu, first author of the paper and a research associate in Salk's Gene Expression Laboratory. This was exactly what they found. When miR25 and miR93 were turned on, cGAS levels were lower. When miR25 and miR93 were inhibited, cGAS levels remained high.
"To follow up this study, we're now investigating the different immune cells that can contribute to cancer anti-tumor immunity," notes Wu.
Image: Salk researchers discover how oxygen-deprived tumors survive body's immune response. Here, visible regions of hypoxia in tumor samples correlate with cell signaling linked to suppressing the immune system. Image courtesy of the Salk Institute.