PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype.
In the present study, we evaluated whether infection of microvascular endothelial cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether PAX2 protein is involved in HHV-8-induced transformation of HMECs. We found that HHV-8 infection induced the expression of both the PAX2 gene and PAX2 protein in HMECs but failed to induce PAX2 protein in HMECs stably transfected with PAX2 antisense (HMEC-AS). HHV-8-infected HMECs but not HMEC-AS acquired proinvasive proadhesive properties, enhanced survival and in vitro angiogenesis, suggesting a correlation between PAX2 expression and the effects triggered by HHV-8 infection. When HMEC-expressing PAX2 by stable transfection with PAX2 sense gene or by HHV-8 infection were implanted in vivo in severe combined immunodeficient (SCID) mice, enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV-8-infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These results suggest that the expression of PAX2 is required for the proangiogenic and proinvasive changes induced by HHV-8 infection in HMECs. In conclusion, HHV-8 infection may activate an embryonic angiogenic program in HMECs by inducing the expression of PAX2 oncogene.
Fonsato
Valentina
V
Department of Internal Medicine, Research Center for Experimental Medicine and Center for Molecular Biotechnology, University of Torino, Turin, Italy.
Buttiglieri
Stefano
S
Deregibus
Maria Chiara
MC
Bussolati
Benedetta
B
Caselli
Elisabetta
E
Di Luca
Dario
D
Camussi
Giovanni
G
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D019288:Herpesvirus 8, Human / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007797:Laminin; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology*; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011509:Proteoglycans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016372:RNA, Antisense; D012514:Sarcoma, Kaposi / Q000473:pathology
D018932:Chemokine CCL2; D004338:Drug Combinations; D007797:Laminin; D051762:PAX2 Transcription Factor; D011509:Proteoglycans; D016372:RNA, Antisense; C059485:matrigel; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt