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.
Department of Internal Medicine, Research Center for Experimental Medicine and Center for Molecular Biotechnology, University of Torino, Turin, Italy.
Valentina
V
Fonsato
Stefano
S
Buttiglieri
Maria Chiara
MC
Deregibus
Benedetta
B
Bussolati
Elisabetta
E
Caselli
Dario
D
Di Luca
Giovanni
G
Camussi
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