Inhibin is a novel paracrine factor for tumor angiogenesis and metastasis

Inhibin is a heterodimeric TGF-β family ligand that is expressed in many cancers and is a selective biomarker for ovarian cancers, however its tumor-specific functions remain unknown. Here we demonstrate that the α subunit of Inhibin (INHA), which is critical for the functionality of dimeric Inhibin A/B, correlates with microvessel density (MVD) in human ovarian tissues and xenografts and is predictive of poor clinical outcomes in multiple cancers. We demonstrate that Inhibin regulated angiogenesis is necessary for metastasis. While Inhibin had no direct impact on tumor cell signaling, both tumor cell-derived and recombinant Inhibin elicit a strong paracrine response from endothelial cells by triggering SMAD1/5 activation and angiogenesis in vitro and in vivo. Inhibin-induced angiogenesis was abrogated via anti-Inhibinα antibodies. The endothelial-specific TGF-β receptor complex comprising ALK1 and endoglin were crucial mediators of Inhibin signaling, offering a molecular mechanism for Inhibin-mediated angiogenesis. These results are the first to define a role for Inhibin in tumor metastasis and vascularization and offer an antibody-based approach for targeting Inhibin therapeutically

http://ift.tt/2GnYXER