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Julia Poland, Dirk Schadendorf, Hermann Lage, Martina Schnölzer, Julio E. Celis, Pranav Sinha
Study of Therapy Resistance in Cancer Cells with Functional Proteome Analysis
Different types of cancer are naturally resistant to
many anticancer drugs. Additionally, these tumours
develop acquired drug resistance, which includes the
classical multidrug resistance (MDR) accompanied by
the synthesis of P-glycoprotein, a member of the superfamily
of ATP-binding cassette (ABC) transporters.
Furthermore, atypical MDR is mediated by several different,
some unkown, mechanisms. To overcome
chemoresistance problems, antineoplastic drugs are
often combined with other modes of therapy,
A model system to study resistance phenomena is the use of chemoresistant and thermoresistant cancer cell lines. We have established chemoresistant cancer cell lines (gastric and pancreatic carcinoma, fibrosarcoma, melanoma) and now thermoresistant cell lines derived from gastric and pancreatic carcinoma cells and their counterparts that were resistant towards daunorubicin (classical MDR) and mitoxantrone (atypical MDR).
Using proteomics, in this paper we evaluate the drug resistance of chemoresistant melanoma cells (parental cell line MeWo and sublines exhibiting drug resistance towards etoposide, cisplatin, fotemustine and vindesine) as a paradigm for analysis of drug resistance phenomena. Additionally, we investigate heat resistance and the interaction of chemoresistance and thermoresistance to identify common pathways using the parental and drug resistant stomach cancer cell lines EPG85-257, EPG85-257RNOV, EPG85-257RDB and their thermoresistant counterparts. Possible implications of differential protein expression will be discussed.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 40, 04/2002
Pages: 221 - 234