Inhibin Is a Novel Paracrine Factor for Tumor Angiogenesis and Metastasis.
Cancer Res
; 78(11): 2978-2989, 2018 06 01.
Article
em En
| MEDLINE
| ID: mdl-29535220
ABSTRACT
Inhibin is a heterodimeric TGFß 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 TGFß 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.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Peptídeos e Proteínas de Sinalização Intercelular
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Inibinas
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Metástase Neoplásica
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Neovascularização Patológica
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article