TGFβ Controls Ovarian Cancer Cell Proliferation

Abstract

There have been no major improvements in the overall survival of ovarian cancer patients in recent decades. Even though more accurate surgery and more effective treatments are available, the mortality rate remains high. Given the differences in origin and the heterogeneity of these tumors, research to elucidate the signaling pathways involved is required. The Transforming Growth Factor (TGFβ) family controls different cellular responses in development and cell homeostasis. Disruption of TGFβ signaling has been implicated in many cancers, including ovarian cancer. This article considers the involvement of TGFβ in ovarian cancer progression, and reviews the various mechanisms that enable the TGFβ signaling pathway to control ovarian cancer cell proliferation. These mechanistic explanations support the therapeutic use of TGFβ inhibitors in ovarian cancer, which are currently in the early phases of development.

Keywords: IGF1R; TGFβ; ovarian cancer; proliferation.

Figure 1

The level of phosphorylated and active SMAD2 (pSMAD2) staining is correlated with poor patient outcome. (A) pSMAD2 staining of normal human Fallopian tube epithelium. 400×, bar 100 µm. Staining was performed as previously described [25]; (B) pSMAD2 staining of a high-grade serous human tumor. 400×, bar 100 µm. Staining was performed as previously described [25]; (C) Correlation between pSMAD2 levels in tissue microarray from high-grade serous ovarian patients and overall patient survival. The tissue microarray (TMA) comprised triplet cores from ovarian tumors resected between 1992 and 2007 at the Bellvitge Hospital (Barcelona, Spain). The study protocol was cleared by the hospital’s Ethics Committee and signed informed consent was obtained from each patient. A total of 27 high-degree serous paraffin-embedded epithelial ovarian tumor specimens were represented and available for analysis on the TMA. All patients were treated using primary surgery and samples were collected before any radiotherapy or chemotherapy. This study included patients aged 30–88 years, with 79% aged 50–70 years. We observed no segregation due to age in our parameters. The Pearson correlation coefficient was used for statistical analysis.