Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44

J Biol Chem. 2001 Jun 15;276(24):20809-12. doi: 10.1074/jbc.C100140200. Epub 2001 Apr 24.

Abstract

Elevated tumor cyclooxygenase (COX-2) expression is associated with increased angiogenesis, tumor invasion, and suppression of host immunity. We have previously shown that genetic inhibition of tumor COX-2 expression reverses the immunosuppression induced by non-small cell lung cancer (NSCLC). To assess the impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were transduced with a retroviral vector expressing the human COX-2 cDNA in the sense (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S clones expressed significantly more COX-2 protein, produced 10-fold more prostaglandin E(2), and demonstrated an enhanced invasive capacity compared with control vector-transduced or parental cells. CD44, the cell surface receptor for hyaluronate, was overexpressed in COX-2-S cells, and specific blockade of CD44 significantly decreased tumor cell invasion. In contrast, COX-2-AS clones had a very limited capacity for invasion and showed diminished expression of CD44. These findings suggest that a COX-2-mediated, CD44-dependent pathway is operative in NSCLC invasion. Because tumor COX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Antigens, CD / physiology
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / physiology*
  • Hyaluronic Acid / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Membrane Proteins
  • Neoplasm Invasiveness
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Recombinant Proteins / metabolism
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Hyaluronan Receptors
  • Isoenzymes
  • Membrane Proteins
  • Recombinant Proteins
  • Hyaluronic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone