Frequent infection of human cancer xenografts with murine endogenous retroviruses in vivo.
Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies.
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. a.naseer.1@research.gla.ac.uk.
Asif
A
Naseer
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. anne.terry@glasgow.ac.uk.
Anne
A
Terry
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. kathryn.gilroy@glasgow.ac.uk.
Kathryn
K
Gilroy
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. anna.kilbey@glasgow.ac.uk.
Anna
A
Kilbey
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. ciorsdaidh.watts@glasgow.ac.uk.
Ciorsdaidh
C
Watts
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. annie.mackay@glasgow.ac.uk.
Nancy
N
Mackay
School of Veterinary Medicine, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. margaret.bell@glasgow.ac.uk.
Margaret
M
Bell
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, G61 1BD Glasgow, UK. s.mason@beatson.gla.ac.uk.
Susan
S
Mason
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, G61 1BD Glasgow, UK. k.blyth@beatson.gla.ac.uk.
Karen
K
Blyth
School of Veterinary Medicine, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. ewan.cameron@glasgow.ac.uk.
Ewan
E
Cameron
Molecular Oncology Laboratory, MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Bearsden Road, G61 1QH Glasgow, UK. james.neil@glasgow.ac.uk.
James C
JC
Neil
D000818:Animals; D020077:Endogenous Retroviruses / Q000302:isolation & purification*; D064593:Heterografts / Q000821:virology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000821:virology*; D011446:Prospective Studies