title: PDGF beta targeting in cervical cancer cells suggest a fine-tuning of compensatory signalling pathways to sustain tumourigenic stimulation.
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.
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. I. Chiricuta", Cluj-Napoca, Romania.
authors.forename: Oana Mihaela
authors.initials: OM
authors.lastname: Tudoran
authors.forename: Olga
authors.initials: O
authors.lastname: Soritau
authors.forename: Loredana
authors.initials: L
authors.lastname: Balacescu
authors.forename: Laura
authors.initials: L
authors.lastname: Pop
authors.forename: Guillaume
authors.initials: G
authors.lastname: Meurice
authors.forename: Simona
authors.initials: S
authors.lastname: Visan
authors.forename: Staffan
authors.initials: S
authors.lastname: Lindberg
authors.forename: Alexandru
authors.initials: A
authors.lastname: Eniu
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Balacescu
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
mesh_terms: D000077214:Becaplermin; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin
keywords: PDGFBB; cervical cancer; microarray; molecular signalling