Premium
A recombinant endogenous retrovirus amplified in a mouse neuroblastoma is involved in tumor growth in vivo
Author(s) -
Pothlichet Julien,
Heidmann Thierry,
Mangeney Marianne
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21935
Subject(s) - immunoediting , biology , endogenous retrovirus , retrovirus , endogeny , provirus , virology , neuroblastoma , recombinant dna , immune system , microbiology and biotechnology , cell culture , cancer research , virus , immunology , gene , genetics , immunotherapy , genome , endocrinology
The theory of immunoediting postulates that tumor cells exhibit a reduced immunogenicity to escape eradication by the host immune system. It has been proposed that endogenous retroviruses—provided that they are active—could play a role in this process, via the immunosuppressive domain carried by their envelope protein. Here, we demonstrate that the Neuro‐2a tumor cell line—originating from a spontaneous A/J mouse neuroblastoma—produces an infectious retrovirus that most probably results from a recombination event between 2 mouse endogenous retroviral elements. This Neuro‐2a‐associated recombinant retrovirus derives from the unique ecotropic provirus located at the Emv‐1 locus, but with a gag sequence conferring B‐tropism, thus allowing its high‐level amplification in Neuro‐2a cells. We show that knocking down ‐by RNA interference‐ this endogenous retrovirus in Neuro‐2a cells has no effect on the transformed phenotype of the cells, but results in delayed tumor growth and prolonged animal survival, following engraftment of the cells into immunocompetent mice. Recombination between endogenous retroviruses, amplification of the resulting element and high‐level expression of its immunosuppressive activity are therefore likely steps of an immunoediting process, leading to an invading tumor. © 2006 Wiley‐Liss, Inc.