Insulin-like growth factor-I-dependent growth and in vitro chemosensitivity of Ewing's sarcoma and peripheral primitive neuroectodermal tumour cell lines.
Serum-free growth of Ewing's sarcoma (ES) and primitive peripheral neuroectodermal tumour (pPNET) cell lines was achieved by supplementing a basal medium with insulin-like growth factor-I (IGF-I). These cultures were used to investigate the sensitivity of 3 ES (EW-2, RD-ES, SK-ES-1) and 3 pPNET (SIM-1, KAL, SAL) cell lines to a panel of anti-tumour agents in short-term (48-h) proliferation assays. Of the four cytostatic drugs included in the currently used multi-drug regimens, cyclophosphamide, doxorubicin and actinomycin-D inhibit the proliferation of the cell lines with high efficacy, whereas the vinca alkaloids were less effective. Cisplatin, etoposide, mitomycin-C and mitoxanthrone were also found to have a high inhibitory activity in this in vitro ES/pPNET system. The most remarkable effect was observed for cytosine arabinoside (ARA-C), which gave a half-maximal inhibition at drug concentrations approximately 5000 times below the clinical peak plasma concentrations (250 micrograms/ml). The ARA-C sensitivity of ES and pPNET cell lines is comparable with the established ARA-C sensitivities of leukaemia-derived cells. The different ES and pPNET cell lines showed a rather uniform response to the different cytostatic drugs with decreased sensitivity of individual pPNET cell lines to vinblastin, ARA-C and mitoxanthrone. Modulation of the IGF-I/IGF-I receptor/IGF-I binding protein system, which seems to constitute an important stimulator of cell growth in neuroectoderm-derived or -related tumours, can be used to enhance the drug sensitivity of the tumour cells in vivo or in vitro therapeutic procedures. According to our results, serum-free conditions for autologous bone marrow purification are expected to result in significantly increased chemosensitivity of ES and pPNET cells in response to anthracyclines and cisplatin.
Hofbauer
S
S
Department of Surgery, University of Vienna, Austria.
Hamilton
G
G
Theyer
G
G
Wollmann
K
K
Gabor
F
F
D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D003561:Cytarabine; D007334:Insulin-Like Growth Factor I