Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation

Herrera, B., van Dinther, M., ten Dijke, P. and Inman, G. J. (2009) Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Research, 69(24), pp. 9254-9262. (doi: 10.1158/0008-5472.CAN-09-2912) (PMID:19996292) (PMCID:PMC2892305)

Abstract

Bone morphogenetic proteins (BMPs) act as central regulators of ovarian physiology and may be involved in ovarian cancer development. In an effort to understand these processes we characterized TGFβ/BMP receptor and Smad expression in immortalised ovarian surface epithelial cells (IOSE) and a panel of ovarian cancer cell lines. These studies prompted us to evaluate the potential role of BMP9 signalling in ovarian cancer. Using siRNA, ligand trap, inhibitor and ligand stimulation approaches we demonstrate that BMP9 acts as a proliferative factor for IOSE and ovarian cancer cell lines, signalling predominantly via an ALK2/Smad1/Smad4 pathway rather than via ALK1, the major BMP9 receptor in endothelial cells. Importantly, we find that some ovarian cancer cell lines have gained autocrine BMP9 signalling which is required for proliferation. Furthermore, immunohistochemistry analysis of an ovarian cancer tissue microarray reveals that approximately 25% of epithelial ovarian cancers express BMP9 whereas normal human OSE specimens do not. Our data indicate that BMP9 signalling via ALK2 may be a novel therapeutic target in ovarian cancer.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Herrera, Dr Blanca and Inman, Professor Gareth
• Authors: Herrera, B., van Dinther, M., ten Dijke, P., and Inman, G. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 0008-5472
• ISSN (Online): 1538-7445