PDGF beta targeting in cervical cancer cells suggest a fine‐tuning of compensatory signalling pathways to sustain tumourigenic stimulation

Journal of Cellular and Molecular Medicine

Oana Mihaela Tudoran⁴  Olga Soritau⁴  Loredana Balacescu⁴  Laura Pop²  Guillaume Meurice³  Simona Visan⁴  Staffan Lindberg¹  Alexandru Eniu⁴  Ulo Langel¹  Ovidiu Balacescu⁴ 

[1] Department of Neurochemistry, Stockholm University, Stockholm, Sweden;Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy, Cluj-Napoca, Romania;Bioinformatic Core Facility, Institut Gustave Roussy, Villejuif, Paris, France;Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca, Romania

关键词: PDGFBB;    cervical cancer;    microarray;    molecular signalling;   

DOI  :  10.1111/jcmm.12449

来源: Wiley

【 摘 要 】

Abstract

The platelet-derived growth factor (PDGF) signalling pathway has been reported to play an important role in human cancers by modulating autocrine and paracrine processes such as tumour growth, metastasis and angiogenesis. Several clinical trials document the benefits of targeting this pathway; however, in cervical cancer the role of PDGF signalling in still unclear. In this study, we used siRNA against PDGF beta (PDGFBB) to investigate the cellular and molecular mechanisms of PDGFBB signalling in Ca Ski and HeLa cervical cancer cells. Our results show that PDGFBB inhibition in Ca Ski cells led to rapid alterations of the transcriptional pattern of 579 genes, genes that are known to have antagonistic roles in regulating tumour progression. Concomitantly, with the lack of significant effects on cervical cancer cells proliferation, apoptosis, migration or invasion, these findings suggests that cervical cancer cells shift between compensatory signalling pathways to maintain their behaviour. The observed autocrine effects were limited to cervical cancer cells ability to adhere to an endothelial cell (EC) monolayer. However, by inhibiting PDGFBB on cervical cells, we achieved reduced proliferation of ECs in co-culture settings and cellular aggregation in conditioned media. Because of lack of PDGF receptor expression on ECs, we believe that these effects are a result of indirect PDGFBB paracrine signalling mechanisms. Our results shed some light into the understanding of PDGFBB signalling mechanism in cervical cancer cells, which could be further exploited for the development of synergistic anti-tumour and anti-angiogenic therapeutic strategies.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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