The ability in adhesion and invasion of drug-resistant human glioma cells

J Exp Clin Cancer Res. 2000 Sep;19(3):357-62.

Abstract

Drug-resistance is critical in treating malignant tumors, and a variety of treatments are given to control it. Little study has been done, however, on biological changes in tumor cell activity in the course of acquiring drug-resistance. We used a glioma cell line to study changes in cell adhesion and invasion on acquiring drug-resistance. Human glioma culture cell line IN157 was used to establish the cell lines resistant to etoposide (VP-16), vincristine sulfate (VCR), and doxorubicin hydrochloride (DOX). Expressions of integrin alpha2, alpha3, alpha5, and beta1, neuronal cell adhesion molecule (NCAM), and matrix metalloproteinases (MMPs) were examined by flow cytometry. In drug-resistant cells, integrin expression was enhanced and NCAM expression was reduced. Adhesions to the extracellar matrix (ECM) proteins (laminin, fibronectin or type IV collagen) were studied. The adhesive ability of all cell lines increased in a concentration-dependent manner. Adhesion of drug-resistant cells was significantly stronger than that of IN157. The cell invasion of drug-resistant cell lines to the basal membrane was significantly lower than that of IN157. The cell invasion of IN157 was significantly suppressed by adding anti-NCAM antibody. In the case of IN157 with the acquisition of drug-resistance, an increase in the expression of integrins may have enhanced the adhesion to ECM proteins. This finding may be concerned with the decreased activity of drug-resistant cell lines in invading the basement membrane. NCAM expression in drug-resistant cell lines was reduced and anti-NCAM antibody abated invasion of IN157, suggesting that NCAM is involved in IN157 invasion.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Cell Adhesion / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm
  • Etoposide / pharmacology
  • Extracellular Matrix Proteins / metabolism
  • Flow Cytometry
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Neoplasm Proteins / metabolism
  • Neural Cell Adhesion Molecules / analysis
  • Neural Cell Adhesion Molecules / metabolism
  • Nimustine / pharmacology*
  • Tumor Cells, Cultured
  • Vincristine / pharmacology*

Substances

  • Extracellular Matrix Proteins
  • Neoplasm Proteins
  • Neural Cell Adhesion Molecules
  • Nimustine
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Matrix Metalloproteinases