Characterization of the typical multidrug resistance profile in human uveal melanoma cell lines and in mouse liver metastasis derivatives

Melanoma Res. 2005 Aug;15(4):257-66. doi: 10.1097/00008390-200508000-00005.

Abstract

Uveal melanoma is the most common intraocular malignancy. To study its biology, stable cell lines provide a useful tool, but these are very difficult to obtain. A stable and rapidly growing human choroidal melanoma cell line composed of pure epithelioid cells was established and maintained for at least 4 years. In vivo transplantation into BALB/cByJ nude mice induced vascularized tumours at the injection sites. Interestingly, two of three cases produced a liver metastasis. Other uveal melanoma cell lines displaying different morphological aspects were also obtained. To avoid the bias due to uncertain immunologically based staining approaches, several methods were juxtaposed to establish the multidrug resistance (MDR) profile. All the uveal melanomas studied expressed significant levels of the MDR-related MDR1, MRP1 (MDR-related protein 1) and LRP/MVP (lung resistance protein/major vault protein) messenger RNAs (mRNAs), produced their corresponding proteins and were able to functionally extrude daunomycin. When compared with the established MEWO skin melanoma cell line, our data showed that both primary and metastatic uveal melanomas intrinsically expressed the typical MDR phenotype, which precludes the use of any anticancer drugs known to be substrates of MDR-related proteins to treat the disease. Moreover, it appears that the metastasizing process does not change the status of the MDR phenotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism*
  • Daunorubicin / pharmacology
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Neoplasm
  • Humans
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / secondary*
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / metabolism*
  • Uveal Neoplasms / pathology
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Antibiotics, Antineoplastic
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Daunorubicin