Alteration of melanoma cell phenotype following in vitro culturing and exposure to cytostatic agents.
Pleiotropic drug resistance is supposed to be associated with a particular tumor cell phenotype, defined by certain plasma membrane glycolipids. Therefore we wondered how far chemosensitivity in vitro correlates with phenotypic characteristics of melanoma cells, which are known to be highly refractory to cytocidal agents. 13 monolayer cell cultures of metastatic melanoma derived from 9 patients were tested with 12 monoclonal antibodies against constitutive, differentiation- and progression-associated antigens. In parallel these primary cell cultures were subjected to a proliferation inhibition assay in the presence of dacarbazine, cis-platinum and carboplatinum. Transferring melanoma cells from original tissue-suspensions into short-term monolayer cultures caused a change in the expression of certain tumor antigens in 54% of 104 assays. In addition, the incubation of the cultivated cells with various cytostatic agents caused them to alter their phenotype in 32% of 128 assays. Irrespective of the spontaneous or induced changes in the antigen patterns, cells lacking HLA-ABC and/or HLA-DR were inhibited more markedly by cytostatic agents as compared to those other cells expressing these antigens. The data suggest, that pretherapeutic determination of tumor cell phenotype may provide clinically useful information for therapeutic decisions in patients with metastatic melanoma.
Engel
E
E
Hämatologisch-onkologische Praxis Altona, Hamburg, FRG.
Kleeberg
U R
UR
Dietel
M
M
Bröcker
E B
EB
Carrel
S
S
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin; D002945:Cisplatin / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis; D003606:Dacarbazine / Q000494:pharmacology; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D058950:Melanoma-Specific Antigens; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006680:HLA Antigens; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D003606:Dacarbazine; D016190:Carboplatin; D002945:Cisplatin