Human cytomegalovirus infection of tumor cells downregulates NCAM (CD56): a novel mechanism for virus-induced tumor invasiveness.
Pathologic data indicate that human cytomegalovirus (HCMV) infection might be associated with the pathogenesis of several human malignancies. However, no definitive evidence of a causal link between HCMV infection and cancer dissemination has been established to date. This study describes the modulation of the invasive behavior of NCAM-expressing tumor cell lines by HCMV. Neuroblastoma (NB) cells, persistently infected with the HCMV strain AD169 (UKF-NB-4AD169 and MHH-NB-11AD169), were added to endothelial cell monolayers and adhesion and penetration kinetics were measured. The 140- and 180-kDa isoforms of the adhesion receptor NCAM were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides or NCAM transfection. HCMV infection profoundly increased the number of adherent and penetrated NB, compared to controls. Surface expression of NCAM was significantly lower on UKF-NB-4AD169 and MHH-NB-11AD169, compared to mock-infected cells. Western-blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoform. An inverse correlation between NCAM expression and adhesion capacity of NB has been shown by antisense and transfection experiments. We conclude that HCMV infection leads to downregulation of NCAM receptors, which is associated with enhanced tumor cell invasiveness.
Blaheta
Roman A
RA
Zentrum der Hygiene, Institut für Medizinische Virologie, Germany.
Beecken
Wolf-Dietrich
WD
Engl
Tobias
T
Jonas
Dietger
D
Oppermann
Elsie
E
Hundemer
Michael
M
Doerr
Hans Wilhelm
HW
Scholz
Martin
M
Cinatl
Jindrich
J
D001483:Base Sequence; D019002:CD56 Antigen / Q000235:genetics*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000473:pathology*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009447:Neuroblastoma; D016376:Oligonucleotides, Antisense; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014471:Umbilical Veins
D019002:CD56 Antigen; D017931:DNA Primers; D016376:Oligonucleotides, Antisense