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.