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Article

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Accepted version

Publication date

2016-10-15

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/120451

The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels

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https://doi.org/10.1002/ijc.30233

Abstract

In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition.

Subject

Factors de creixement, Càncer d'ovari, Proliferació cel·lular, Cèl·lules epitelials, Receptors d'insulina

Subject (English)

Growth factors, Ovarian cancer, Cell proliferation, Epithelial cells, Insulin receptors

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citation

ALSINA SANCHÍS, Elisenda, et al. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels. International Journal of Cancer. 2016. Vol. 139, num. 8, pags. 1894-1903. ISSN 0020-7136. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/120451

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