Tumor control by human cytomegalovirus in a murine model of hepatocellular carcinoma.
Although viruses can cause cancer, other studies reported the regression of human tumors upon viral infections. We investigated the cytoreductive potential of human cytomegalovirus (HCMV) in a murine model of human hepatocellular carcinoma (HCC) in severe-immunodeficient mice. Infection of HepG2 cells with HCMV resulted in the absence of tumor or in a limited tumor growth following injection of cells subcutaneously. By contrast all mice injected with uninfected HepG2 cells and with HepG2 cells infected with UV-treated HCMV did develop tumors without any significant restriction. Analysis of tumors indicated that in mice injected with HCMV-infected-HepG2 cells, but not in controls, a restricted cellular proliferation was observed parallel to a limited activation of the STAT3-cyclin D1 axis, decreased formation of colonies in soft agar, and activation of the intrinsic apoptotic pathway. We conclude that HCMV can provide antitumoral effects in a murine model of HCC which requires replicative virus at some stages that results in limitation of tumor cell proliferation and enhanced apoptosis mediated through the intrinsic caspase pathway.
Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France.
Amit
A
Kumar
Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France.
Laurie
L
Coquard
Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France.
Sébastien
S
Pasquereau
Department of Pathology, CHRU Besançon , Besançon, France.
Laetitia
L
Russo
Department of Pathology, CHRU Besançon , Besançon, France.
Séverine
S
Valmary-Degano
Department of Medical Oncology, INSERM UMR1098, EFS Bourgogne Franche-Comté , Besançon, France.
Christophe
C
Borg
Department of Virology, Pathogens & Inflammation Laboratory, UPRES EA4266, SFR FED 4234, CHU Dijon , Dijon, France.
Pierre
P
Pothier
Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France.
Georges
G
Herbein