Integration of adeno-associated virus 2 DNA in human MKR melanoma cells induces a peptide with oncosuppressive properties.
Integration of adeno-associated virus type 2 (AAV2) DNA into the genome of the human MKr melanoma cell line grossly alters the cellular phenotype of these cells. Cultures derived from AAV DNA-harboring single cells share various similarities with normal cells in culture, and a considerable number of clones show signs of cellular senescence and terminal differentiation. Medium conditioned by such terminally differentiating cells contains a small cytokine-like factor (AAV-induced factor [AIF]). The factor was characterized as peptide, which influences cell adhesion and appears to exist in forms of different activity connected by a trypsin-like cleavage site. It modulates cell growth in opposite ways: proliferation of tumor-derived cells is inhibited and fibroblasts are stimulated. The observations suggest that integration of AAV may result in cytokine induction and thus can indirectly affect growth of distant AAV-free target cells in a paracrine or endocrine manner. This is of interest with regard to anti-oncogenic properties of AAV and may also imply the possibility of AAV pathogenicity.
Bantel-Schaal
U
U
Deutsches Krebsforschungszentrum Heidelberg, Angewandte Tumorvirologie F0400, Heidelberg, Germany. u.bantel-schaal@dkfz-heidelberg.de
D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000229:Dependovirus / Q000378:metabolism*; D019286:Endopeptidase K / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010641:Phenotype; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D014357:Trypsin; D019286:Endopeptidase K