Human cytomegalovirus infection alters PC3 prostate carcinoma cell adhesion to endothelial cells and extracellular matrix.
The genome and antigens of human cytomegalovirus (HCMV) are frequently found in prostatic carcinoma. However, whether this infection is causative or is an epiphenomenon is not clear. We therefore investigated the ability of HCMV to promote metastatic processes, defined by tumor cell adhesion to the endothelium and extracellular matrix proteins. Experiments were based on the human prostate tumor cell line PC3, either infected with the HCMV strain Hi (HCMV(Hi)) or transfected with cDNA encoding the HCMV-specific immediate early protein IEA1 (UL123) or IEA2 (UL122). HCMV(Hi) upregulated PC3 adhesion to the endothelium and to the extracellular matrix proteins collagen, laminin, and fibronectin. The process was accompanied by enhancement of beta(1)-integrin surface expression, elevated levels of integrin-linked kinase, and phosphorylation of focal adhesion kinase. IEA1 or IEA2 did not modulate PC3 adhesion or beta(1)-integrin expression. Based on this in vitro model, we postulate a direct association between HCMV infection and prostate tumor transmigration, which is not dependent on IEA proteins. Integrin overexpression, combined with the modulation of integrin-dependent signalling, seems to be, at least in part, responsible for a more invasive PC3(Hi) tumor cell phenotype. Elevated levels of c-myc found in IEA1-transfected or IEA2-transfected PC3 cell populations might promote further carcinogenic processes through accelerated cell proliferation.
Blaheta
Roman A
RA
Zentrum der Chirurgie, Klinik für Urologie und Kinderurologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Weich
Eva
E
Marian
Dana
D
Bereiter-Hahn
Jürgen
J
Jones
Jon
J
Jonas
Dietger
D
Michaelis
Martin
M
Doerr
Hans Willhelm
HW
Cinatl
Jindrich
J
D000941:Antigens; D000951:Antigens, Neoplasm; D002277:Carcinoma / Q000473:pathology* / Q000821:virology*; D002448:Cell Adhesion; D003586:Cytomegalovirus Infections; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000821:virology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000941:Antigens; D000951:Antigens, Neoplasm; D019012:Integrin beta1; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C038170:interspecific embryonic antigen-1; C038171:interspecific embryonic antigen-2