Study of the development of chemoresistance in melanoma cell lines using proteome analysis

Pranav Sinha, Julia Poland, Sandro Kohl, Martina Schnölzer, Heike Helmbach, Gero Hütter, Hermann Lage, Dirk Schadendorf, H Helmbach

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Malignant melanomas have poor prognosis since treatment with anti-neoplastic agents is mostly ineffective. The biological mechanisms of this strong intrinsic therapy resistance are unknown. In order to identify new molecular factors potentially associated with the drug-resistant phenotype of malignant melanoma, a panel of human melanoma cell variants exhibiting low and high levels of resistance to four commonly used anticancer drugs in melanoma treatment, i.e., vindesine, etoposide, cisplatin, and fotemustine, was characterized using proteomic tools (two-dimensional electrophoresis for protein fractionation and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry for protein identification). In the neutral and weak acidic milieu (pH 4.0-8.0) a total number of 14 proteins showed alterations in expression whereas 20 proteins were differentially expressed in the basic milieu (pH 8.0-11.0). Besides proteins with unknown physiologic function, several factors were identified that show chaperone activity. Moreover, proteins involved in drug detoxification, metabolism, and regulation of apoptotic pathways could be identified. The possible role of these proteins in the development of chemoresistance is discussed, although detailed functional tests with these proteins have still to be performed. Nevertheless, it is clear that this proteomic approach for studying chemoresistance phenomena is a prerequisite before further investigation can yield insight into the biology and development of drug resistance in malignant melanoma.

Original languageEnglish
Pages (from-to)2386-404
Number of pages19
JournalElectrophoresis
Volume24
Issue number14
DOIs
Publication statusPublished - Jul 2003

Keywords

  • Antineoplastic Agents
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydrogen-Ion Concentration
  • Melanoma
  • Molecular Chaperones
  • Neoplasm Proteins
  • Proteomics

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