Expression of the HOXA9 gene in epithelial ovarian cancer (EOC) cells promotes a microenvironment that allows for tumor growth and results in poor outcomes for patients, researchers have discovered.
Unlike many other types of cancers, EOC rarely spreads by means of the bloodstream, explain Honami Naora, of The University of Texas MD Anderson Cancer Center in Houston, Texas, and colleagues in their report for The Journal of Clinical Investigation. EOC cells typically shed into the peritoneal fluid and implant on the mesothelial linings of peritoneal surfaces that overlie connective and adipose tissues. Approximately 70% of women with EOC present with disease that involves the peritoneal cavity.
Until the recent study, the mechanisms that enable EOC cells to adapt readily to the peritoneal environment were poorly understood. Although tumor growth is dependent upon interactions between cancer cells and stromal cells (cells that make up certain types of connective tissue), and stromal cells can stimulate growth of tumor cells, whether tumor cells can influence stroma has been unclear.
Now, however, Naora’s team has found that HOXA9 expression in ovarian cancer cells is associated with poor survival in mice and in humans, and causes those cells to produce a protein called TGF-β. This protein, in turn, induces the surrounding noncancerous cells to create an environment that supports the tumor. Because blocking TGF-β expression in the cancer cells significantly reduced tumor growth, the investigators proposed that drugs targeting TGF-β have potential as a treatment for ovarian cancer.