# Inhibin function in tumor angiogenesis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $342,331

## Abstract

Ovarian cancer is among the most devastating of gynecological cancers primarily impacting postmenopausal
women. Induction of angiogenesis, the process of generating and remodeling blood vessels, is a critical
requirement for tumor growth and metastasis in multiple cancers including ovarian, leading to the use anti-
angiogenic agents in the clinic. However side effects and toxicities can limit their use. Thus there remains a
need to identify cancer specific, safe ways to control angiogenesis in ovarian cancer. Inhibin is a unique TGF-β
family member whose levels are extremely low in normal post-menopausal women. However Inhibin is an
established biomarker for ovarian cancers with unknown functions. Our preliminary studies show that Inhibin
expression is regulated by hypoxia, a well-appreciated regulator of tumor angiogenesis. We find that Inhibin
exhibits paracrine effects on the endothelium by increasing angiogenesis in vitro and in vivo. Mechanistically,
Inhibin requires the endothelial specific receptors Endoglin and Alk1 to induce angiogenesis. Since Inhibin is
expressed in ovarian cancers, but present at low systemic levels in normal post-menopausal women we will
examine Inhibin as a potential novel angiogenic target for cancer the mechanism of action. The hypothesis to
be tested is that blocking tumoral Inhibin, a novel ligand for endothelial specific TGF-β receptors, and a product
of the hypoxia adaptive response that promotes angiogenesis will result in suppression of tumor angiogenesis.
The specific aims are: 1) To test if blocking Inhibin has therapeutic anti-angiogenic effects in ovarian cancer
alone or in combination with current anti-angiogenic therapies. 2) To delineate the mechanism of Inhibin
induced endothelial cell remodeling and angiogenesis using a combination of cell signaling, biochemical and
biophysical approaches to test Inhibin as a direct novel ligand for endothelial receptors endoglin and Alk1 and
identify novel signaling targets of Inhibin using transcriptomics. 3) To define hypoxia mechanisms regulating
Inhibin expression. I believe that these investigations into Inhibin-mediated angiogenesis will provide the first
insights into previously unknown functions for Inhibin that is broadly expressed in cancer and provide new
targets to safely treat angiogenesis in cancer.

## Key facts

- **NIH application ID:** 9957067
- **Project number:** 5R01CA219495-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Mythreye Karthikeyan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,331
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957067

## Citation

> US National Institutes of Health, RePORTER application 9957067, Inhibin function in tumor angiogenesis (5R01CA219495-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9957067. Licensed CC0.

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