Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells.
The survival of patients affected by cutaneous melanoma has improved dramatically in the last 10 years, because of earlier diagnosis. Despite this, the therapeutic results obtained in metastatic melanoma (MM) are very disappointing due to its poor responsiveness to cytotoxic agents. In this type of solid tumor, tumor chemosensitivity assays have been suggested to be an important tool to predict clinical responsiveness to therapy. Metastatic melanoma cells (MMCs) were obtained from subcutaneous melanoma metastases of five patients and cultured for several consecutive passages. An immunofluorescence and an electron microscopic study were performed in order to establish the ultrastructural and physiopathological features of MMCs. A sulphorodamine-B test was used to measure in vitro sensitivity of MMCs to temozolomide, cisplatin, vindesine, taxol and interpheron alpha-2a. Following a 72 h exposure, maximum activity was obtained with vindesine (median inhibitory concentration, IC(50), 0.23 nM) and taxol (median IC(50) 0.31 nM). Cisplatin median IC(50) values were higher (4.6 microM) than taxol and vindesine, but still in the range of clinically achievable plasma concentrations. Temozolomide inhibited cell proliferation only at very high concentrations (median IC(50) 228 microM). No significant cell growth inhibitory effects (<or=25%) were observed with interferon alpha-2a concentrations up to 8000 IU/ml. MMCs expressed progression markers typical of cutaneous metastatic melanoma and showed poor sensitivity in vitro to most anticancer drugs tested, including temozolomide.
Prignano
F
F
Department of Dermatological Sciences, University of Florence, Via Degli Alfani n.37, 50121 Florence, Italy.
Coronnello
M
M
Pimpinelli
N
N
Cappugi
P
P
Mini
E
E
Giannotti
B
B
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D002478:Cells, Cultured; D002945:Cisplatin / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D020128:Inhibitory Concentration 50; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008545:Melanoma / Q000473:pathology* / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use; D011994:Recombinant Proteins; D000077204:Temozolomide; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine; D017239:Paclitaxel; D002945:Cisplatin; D014751:Vindesine; D000077204:Temozolomide