Transforming Growth Factor-Beta-Induced Protein (TGFBI)/(βig-H3): A Matrix Protein with Dual Functions in Ovarian Cancer

Transforming growth factor-beta-induced protein (TGFBI, also known as beta ig-H3 and keratoepithelin) is an extracellular matrix protein that plays a role in a wide range of physiological and pathological conditions including diabetes, corneal dystrophy and tumorigenesis. Many reports indicate that beta ig-H3 functions as a tumor suppressor. Loss of beta ig-H3 expression has been described in several cancers including ovarian cancer and promoter hypermethylation has been identified as an important mechanism for the silencing of the TGFBI gene. Our recent findings that beta ig-H3 is down-regulated in ovarian cancer and that high concentrations of beta ig-H3 can induce ovarian cancer cell death support a tumor suppressor role. However, there is also convincing data in the literature reporting a tumor-promoting role for beta ig-H3. We have shown beta ig-H3 to be abundantly expressed by peritoneal cells and increase the metastatic potential of ovarian cancer cells by promoting cell motility, invasion, and adhesion to peritoneal cells. Our findings suggest that beta ig-H3 has dual functions and can act both as a tumor suppressor or tumor promoter depending on the tumor microenvironment. This article reviews the current understanding of beta ig-H3 function in cancer cells with particular focus on ovarian cancer.