Angiogenesis Modulators Expression in Culture Cell Lines Positives for HPV-16 Oncoproteins

Altered angiogenesis response is observed in patients with cervical cancer. In this study we examined whether Human Papilloma Virus (HPV) positive epithelial cells are able to produce angiogenic modulators. When added to human umbilical vein endothelial cells (HUVEC) the media conditioned by HPV-16 positive cells was able to induce proliferation, whereas a contrary effect was observed for media derived from non-tumorigenic keratinocytes. The analyses of angiogenesis modulator's mRNA levels result in a decrease of the antiangiogenic factors TSP-1 and 2 in HPV-16 positive cells. In contrast the expression of the pro-angiogenic molecules: bFGF, IL-8, TGF-β, TNFα, and VEGF were higher in these cells as compared to control keratinocytes. Furthermore the pattern of VEGF isoforms observed in the cells positive for the viral genome point to a preferential induction of the VEGF189 isoform. We therefore conclude that cervical cancer cells expressing HPV-16 genome are able to contribute to the pro-angiogenic response that might support tumor growth and invasion of the surrounding tissues.