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 once-suppressive potential and inhibit proliferation of cells derived from malignant human tumors in cult ure. Growth inhibition of human melanoma cells can be achieved when the cel ls are infected with these viruses but continues subsequent to infection wh en viral DNA is chromosomally integrated. Integration of AAV2 DNA into the genome of the human melanoma cell line MKr alters the cellular phenotype to wards that of diploid cells in culture, and leads to density-arrested growt h, strong reduction of the ability to form colonies from single cells and t o an increased number of terminally differentiating cultures. The present s tudy aimed at the question whether the altered growth properties were retai ned upon prolonged co-cultivation with fibroblasts, i.e. under conditions t hat occur in invasive growth and colonization of distant tissues. The resul ts show that despite the known possibility of growth stimulation by fibrobl asts the potential of melanoma cells to proliferate and the potential to fu rther scatter in the fibroblast cultures remain limited when AAV DNA is int egrated. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.