Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

Br J Cancer. 2009 Aug 4;101(3):432-40. doi: 10.1038/sj.bjc.6605185. Epub 2009 Jul 14.

Abstract

Background: Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of treatment failure and mortality in cancer patients.

Methods: We evaluated invasive markers of urokinase plasminogen activator (uPA) and CD44 and multiple drug-resistance (MDR) markers of MDR1 and MRP2 in four epithelial ovarian cancer (EOC) cell lines, primary tumours (n=120) and matched metastatic lesions (n=40) by immunofluoresence labelling. We correlated uPA and CD44 with MDR markers in primary and metastatic cells using confocal microscope. We also investigated the relationship of the expression of uPA, CD44 and MDR1 with various progression parameters.

Results: The coexpression of uPA and CD44 with MDR markers was found in primary and metastatic cells. The overexpression of uPA, CD44 and MDR1 was found in most primary and matched metastatic lesions of EOC, and was significantly associated with tumour stage, grade, residual disease status, relapse and presence of ascites (P<0.05), but not with histology type (P>0.05).

Conclusions: Our results suggest that the overexpression of uPA, CD44 and MRD1 is correlated with EOC progression; both uPA and CD44 are related with drug resistance during EOC metastasis and could be useful therapeutically.

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 / analysis*
  • Adult
  • Aged
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Hyaluronan Receptors / analysis*
  • Microscopy, Confocal
  • Middle Aged
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / analysis*
  • Neoplasm Metastasis
  • Neoplasms, Glandular and Epithelial / chemistry
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / pathology*
  • Urokinase-Type Plasminogen Activator / analysis*

Substances

  • ABCB1 protein, human
  • ABCC2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Hyaluronan Receptors
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Urokinase-Type Plasminogen Activator