Gera, S and Sandeep Kumar, S and Swamy, SN and Bhagat, R and Vadaparty, A and Gawari, R and Bhat, R and Dighe, RR (2019) Follicle-stimulating hormone is an autocrine regulator of the ovarian cancer metastatic niche through notch signaling. In: Journal of the Endocrine Society, 3 (2). pp. 340-357.
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Abstract
The association between the upregulated Notch and FSH signaling and ovarian cancer is well documented. However, their signaling has been investigated independently and only in the primary tumor tissues. The aim of this study was to investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation, formation, and maintenance of disseminated ovarian cancer cells. The roles of Notch and FSH in ovarian cancer pathogenesis were investigated with ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR). FSH upregulated Notch signaling and proliferation in ovarian cancer cells. High levels of FSH were detected in the ascites of patients with serous ovarian adenocarcinoma. Spheroids from the patients' ascites, as well as the spheroids from ovarian cancer cell lines under low attachment culture conditions, expressed FSHb subunit mRNA and secreted the hormone into the medium. In contrast, primary ovarian tumor tissues and cell line monolayers expressed very low levels of FSHb. Ovarian cancer cell spheroids also exhibited higher expression of FSH receptor and Notch downstream genes than their monolayer counterparts. A combination of FSHR and Notch antagonistic antibodies significantly inhibited spheroid formation and cell proliferation in vitro. This study demonstrates that spheroids in ascites express and secrete FSH, which regulates cancer cell proliferation and spheroidogenesis through Notch signaling, suggesting that FSH is an autocrine regulator of cancer metastasis. Furthermore, Notch and FSHR are potential immunotherapeutic targets for ovarian cancer treatment.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of the Endocrine Society |
| Publisher: | Oxford University Press |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | antibody; follitropin; follitropin receptor; messenger RNA; Notch1 receptor; Notch2 receptor; Notch3 receptor; Notch4 receptor, Article; ascites; autocrine effect; cancer cell; cancer tissue; carcinogenesis; cell proliferation; controlled study; female; gene expression; hormone action; hormone release; human; human cell; human tissue; in vitro study; metastasis; mRNA expression level; Notch signaling; ovary adenocarcinoma; OVCAR-3 cell line; OVCAR-4 cell line; priority journal; real time polymerase chain reaction; SK-OV-3 cell line; tumor spheroid |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 25 Oct 2022 10:44 |
| Last Modified: | 25 Oct 2022 10:44 |
| URI: | https://eprints.iisc.ac.in/id/eprint/77569 |
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