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-beta, TNFalpha, 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 VEGF(189) 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.
Bequet-Romero
M
M
Pharmaceutical, Centre for Genetic Engineering and Biotechnology, Havana, C. Habana, 10600, Cuba. monica.bequet@cigb.edu.cu
López-Ocejo
O
O
D043925:Angiogenesis Inducing Agents / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D019700:Thrombospondin 1 / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2
D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; D019700:Thrombospondin 1; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099262:Thrombospondin 2; C068651:E6 protein, Human papillomavirus type 16; C467484:VEGFA protein, human; C059731:oncogene protein E7, Human papillomavirus type 16