Growth properties of a human melanoma cell line are altered by adeno-associated parvovirus type 2

The adeno-associated parvoviruses (AAV) are known for their oncosuppressive activity. This report shows that infection of the human melanoma cell line MKr with AAV-2 leads to chromosomal integration of the viral DNA. The resulting cultures show decrease of saturation density and reduction in their ability to form colonies from single cells and thus to resemble normal cells. After single-cell cloning they may give rise to growth-arrested, terminally differentiating large, multinucleated cells with dendrite-like extensions, large nucleoli and the ability to synthesize melanin pigment. In cultured melanoma cells, melanin synthesis is correlated with cellular senescence, and since senescent cells cease to proliferate and withdraw from the cell cycle, the apparent induction of growth arrest and terminal differentiation in malignant cells by AAV may provide one explanation for the anti-neoplastic activity of these viruses.