American Association for Cancer Research
00085472can172316-sup-187170_3_supp_4610999_p56psl.pdf (14.23 MB)

Figure S1 from Inhibin Is a Novel Paracrine Factor for Tumor Angiogenesis and Metastasis

Download (14.23 MB)
journal contribution
posted on 2023-03-31, 01:24 authored by Priyanka Singh, Laura M. Jenkins, Ben Horst, Victoria Alers, Shrikant Pradhan, Prabhjot Kaur, Tapasya Srivastava, Nadine Hempel, Balázs Győrffy, Eugenia V. Broude, Nam Y. Lee, Karthikeyan Mythreye

(i) Sample images of immunohistochemistry (IHC) using IgG or anti-Inhibina antibody on the same ovarian tumor. (ii) Zoomed in images of regions IHC Fig 1A (Human Ovary Cancer Tissue Microarray, Protein Biotechnologies) of either normal tissue or different ovarian cancer subtypes with Inhibina staining. (iii) Additional examples of CD31 staining with corresponding Inhibina levels in the same cores from tissue array immunolabeled with anti-Inhibina or anti-CD31 antibody. (iv) ELISA for total Inhibin (Inhibina, InhibinA/B) of the CM from indicated cancer cells. Corresponding mRNA values in Fig 1E.





Inhibin is a heterodimeric TGFβ 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 in human ovarian tissues and is predictive of poor clinical outcomes in multiple cancers. We demonstrate that inhibin-regulated angiogenesis is necessary for metastasis. Although 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-inhibin α antibodies. The endothelial-specific TGFβ receptor complex comprising ALK1 and endoglin was a crucial mediator 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.Significance: Inhibin is a predictor of poor patient survival in multiple cancers and is a potential target for antiangiogenic therapies. Cancer Res; 78(11); 2978–89. ©2018 AACR.