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Follicle-Stimulating Hormone Is an Autocrine Regulator of the Ovarian Cancer Metastatic Niche Through Notch Signaling

Sakshi Gera1, Sandeep Kumar S2, Shalini N Swamy2

  • 1Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bengaluru, India.

Journal of the Endocrine Society
|January 26, 2019
PubMed

Insights

Follicle-stimulating hormone (FSH) and Notch signaling interact to drive ovarian cancer progression and metastasis. Targeting FSH and Notch pathways offers a promising strategy for ovarian cancer immunotherapy.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Notch and FSH signaling are linked to ovarian cancer but studied independently.
  • Previous research focused on primary tumor tissues, overlooking disseminated cells.

Purpose of the Study:

  • Investigate the interactive effects of FSH and Notch signaling on ovarian cancer proliferation.
  • Examine the role of these pathways in the formation and maintenance of disseminated ovarian cancer cells.

Main Methods:

  • Utilized ovarian cancer cell lines and specific antibodies against Notch and FSH receptor (FSHR).
  • Analyzed FSH levels in patient ascites and gene expression in spheroids versus monolayers.
  • Assessed the impact of combined FSHR and Notch antagonistic antibodies on spheroid formation and proliferation.

Main Results:

  • FSH upregulated Notch signaling and proliferation in ovarian cancer cells.
  • Ovarian cancer spheroids in ascites expressed and secreted FSH, unlike primary tumors.
  • Combined FSHR and Notch inhibition significantly reduced spheroid formation and proliferation in vitro.

Conclusions:

  • FSH acts as an autocrine regulator of ovarian cancer metastasis via Notch signaling in spheroids.
  • Notch and FSHR are potential targets for ovarian cancer immunotherapy.

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