Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Br J Cancer. 2010 Sep 28;103(7):1008-18. doi: 10.1038/sj.bjc.6605839. Epub 2010 Aug 24.

Abstract

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP).

Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC(50)) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined.

Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC(50)) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression.

Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Aged
  • Animals
  • Basigin / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Disease Progression
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Male
  • Middle Aged
  • Monocarboxylic Acid Transporters / metabolism*
  • Neoplasm Metastasis
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Taxoids / therapeutic use
  • Up-Regulation

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Monocarboxylic Acid Transporters
  • Taxoids
  • Basigin
  • Docetaxel