Cancer cells appear to communicate with each other, activating an internal mechanism that boosts resistance to common chemotherapies and promotes tumor survival, researchers at UC San Diego Health announced Tuesday.

Dr. Maurizio Zanetti, a UCSD School of Medicine professor, had previously found that cancer cells exploit an internal mechanism used by stressed mammalian cells, called the “unfolded protein response,” to communicate with immune cells from bone marrow.

The UPR is activated in response to unfolded or misfolded proteins accumulating in an organelle that carries out several metabolic functions in the cells — and the site where proteins are built, folded and sent for secretion. The UPR can often decide cell death or survival.

In their new paper, published online in the June 6 issue of Science Signaling, Zanetti and his colleagues said cancer cells appear to take the process beyond just affecting bone marrow cells. The cells use what’s called transmissible ER stress to activate a cellular signaling pathway linked to cancer formation.

Jeffrey Rodvold, a member of Zanetti’s lab and first author of the study, said that cells that went through transmissable ER stress better survived nutrient starvation and common chemotherapies.

“In each instance, receiving stress signals caused cells to survive better,” Rodvold said.

Zanetti said researchers and physicians need to consider these changing cellular dynamics in the tumor microenvironment in developing both a better understanding of cancer and more effective treatments.

“We know that tumor cells live in difficult environments, exposed to nutrient deprivation and lack of oxygen, which in principle should restrict tumor growth,” said Zanetti, also a tumor immunologist at the UCSD Moores Cancer Center. “Through stress transmission, tumor cells help neighboring tumor cells to cope with these adverse conditions and eventually survive and acquire growth advantages.”

The study was funded by, among others, the U.S. Department of Defense, the National Institutes of Health, U.S. Department of Veterans Affairs and the Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad.

–City News Service