Unraveling the mechanism that ovarian cancer cells use to change normal cells around them into cells that promote tumor growth has identified several new targets for treatment of this deadly disease.
In the December issue of the American Association for Cancer Research journal Cancer Discovery, a team or researchers from the University of Chicago Medicine and Northwestern University Feinberg School of Medicine show that ovarian cancer cells induce nearby cells to alter their production of three microRNAs—small strands of genetic material that are important regulators of gene expression.
By changing gene expression, microRNAs can modify a cell's function. In this case, they convert normal, healthy fibroblasts into cancer-associated fibroblasts (CAFs). These CAFs pump out chemical signals telling cancer cells to multiply, invade healthy tissues and travel to distant sites in the abdomen. Importantly, by reversing the microRNA signals the researchers were able to cause CAFs to revert to normal fibroblasts.
"These cancer-supporting cells provide a novel and appealing treatment target," said one of the lead authors of the study Ernst Lengyel, MD, PhD, professor in the department of obstetrics and gynecology at the University of Chicago. "Cancer cells mutate rapidly, which enables them to develop drug resistance. But cancer-associated fibroblasts are genetically stable," he said. "Their harmful behavior is driven by the microRNAs. Inhibiting those signals is a new way to fight this disease. It disrupts the cancer's support system and is unlikely to evolve resistance."
"With ovarian cancer," Lengyel added, "we desperately need new treatments. "There have been no new approaches introduced into the clinic for years, and thus no major improvements in patient survival."
Fibroblasts are the primary cellular component of connective tissue. They provide the structural framework for other tissues and aid in wound healing. When fibroblast-dense tissues are infiltrated by cancer cells, however, "intimate cross-talk between fibroblasts and cancer cells" can covert them to cancer-associated fibroblasts, Lengyel said, "shifting them into a new role."