Abstract C6: Molecular and cellular signaling of PDGFB in cervical cancer cells.

Abstract

Abstract Cervical cancer was reported to be the second most common female cancer worldwide, being the third cause of female cancer mortality annually. Romania ranks first among European countries in cervical cancer incidence and mortality raising the national awareness. Cervical cancer is one of the most aggressive gynecological diseases, mainly is due to rapid development of a functional tumor vascular network. In solid tumors, PDGF signalling has been showed to participate in processes such as autocrine stimulation of tumor cell growth, recruitment of tumor stroma and stimulation of angiogenesis. PDGF signaling increases the interstitial fluid pressure, an important drawback in drug administration due to loss of active agents before they reach the tumors. Several studies have showed that targeting PDGF pathways have anti-angiogenic and anti-tumor effects, implying that inhibition of PDGF signaling may improve the efficacy of chemotherapies. However, these studies have been focused on effects on tumor vasculature and mural cells, and less on tumor cells. Moreover, the molecular mechanisms of PDGF signaling in tumor cells have yet to be investigated. Here we report the molecular and cellular effects of PDGFb inhibition of in cervical tumor cells. We used the RNA interference pathway to trigger PDGFb silencing in two HPV16 positive cervical cancer cell lines (Hela, Caski). We investigated the changes in genes expression induced by PDGFb silencing by means of microarray analysis. Transcriptomic analysis revealed 579 genes to be differentially expressed upon PDGFb silencing. Among the top biological functions regulated by these genes are Cell Death and Survival, Cellular Growth and Proliferation, Cardiovascular System Development and Function, Cellular Movement, etc. Cellular investigations on proliferation, apoptosis, and invasion revealed that PDGFb silencing had no effects on cells ability to proliferate nor induced cell death, which suggest that alternative signaling mechanisms are activated to maintain the balance between cell proliferation and apoptosis. This is probably done throughout HPV16 signaling as some of the identified genes are known to be involved in viral infections. We did however observe that PDGFb silencing reduced the invasiveness of cervical cancer cells. Although preliminary, our results could explain the short-term success of antiangiogenic therapies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C6. Citation Format: Oana M. Tudoran, Olga Soritau, Ovidiu Balacescu, Loredana Balacescu, Staffan Lindberg, Ioana Berindan-Neagoe. Molecular and cellular signaling of PDGFB in cervical cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C6.