Use of nude mouse xenografts as preclinical screens: Characterization of xenograft-derived melanoma cell lines

Abstract

Cell lines derived from human melanoma xenografts were characterized for surface markers, karyotype abnormalities, and in vitro drug sensitivity. Xenografts were established using metastatic explants from untreated patients and passaged in nude mice. Cell lines were readily established from melanoma xenografts, and formed colonies when plated in semisolid media. The lines expressed human melanoma-associated and other surface antigens, human lactate dehydrogenase (LDH) isoenzymes, and contained only human chromosomes. They failed to express murine histocompatibility determinants and were negative for murine viruses by mouse antibody production assay. Karyotypes showed abnormalities of chromosomes 3, 6, and 7 similar to other melanomas. In vitro chemosensitivity profiles were compared using cell line and xenograft colony-forming assays. Values were similar for the original xenografts and their cell lines. Xenograft-derived human melanoma lines resemble other melanoma cell lines and primary melanomas with respect to surface antigens and karyotype abnormalities, and are appropriate models for studying in vitro drug sensitivity. When used as a model for transition from solid tumor to cell line, these studies suggest cell lines closely mirror in vitro chemosensitivities of parent tumor cells. However, occasional, unpredictable changes in sensitivity to some drugs occurs during this transition.