Chromosomal integration of adeno-associated parvovirus DNA limits proliferation and dispersal of human MKr melanoma cells in co-cultures with human fibroblasts

Adeno-associated parvoviruses (AAVs) possess onco-suppressive potential and inhibit proliferation of cells derived from malignant human tumors in culture. Growth inhibition of human melanoma cells can be achieved when the cells are infected with these viruses but continues subsequent to infection when viral DNA is chromosomally integrated. Integration of AAV2 DNA into the genome of the human melanoma cell line MKr alters the cellular phenotype towards that of diploid cells in culture, and leads to density-arrested growth, strong reduction of the ability to form colonies from single cells and to an increased number of terminally differentiating cultures. The present study aimed at the question whether the altered growth properties were retained upon prolonged co-cultivation with fibroblasts, i.e. under conditions that occur in invasive growth and colonization of distant tissues. The results show that despite the known possibility of growth stimulation by fibroblasts the potential of melanoma cells to proliferate and the potential to further scatter in the fibroblast cultures remain limited when AAV DNA is integrated.