| Autor: |
Karthikeyan Mythreye, Nam Y. Lee, Eugenia V. Broude, Balázs Győrffy, Nadine Hempel, Tapasya Srivastava, Prabhjot Kaur, Shrikant Pradhan, Victoria Alers, Ben Horst, Laura M. Jenkins, Priyanka Singh |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6509868.v1 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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