Ligation of CM1 enhances apoptosis of lung cancer cells through different mechanisms in conformity with EGFR mutation

Int J Oncol. 2013 Feb;42(2):469-77. doi: 10.3892/ijo.2012.1731. Epub 2012 Dec 7.

Abstract

Although remarkable developments in lung cancer treatments have been made, lung cancer remains the leading cause of cancer mortality worldwide. Epidermal growth factor receptor (EGFR) is occasionally mutated in non-small cell lung cancer and heterogeneity in treatment response results from different EGFR mutations. In the present study, we found that centrocyte/centroblast marker 1 (CM1), previously reported as a possible apoptosis inducer of B lymphoma cells, is expressed on both A549 with wild‑type EGFR and HCC827 with mutant EGFR lung cancer cells. Ligation of CM1 with anti-CM1 mAb enhanced apoptosis in both lung cancer cell lines through generation of reactive oxygen species (ROS) and disruption of mitochondrial membrane potential, however, the signaling mechanisms differed from each other. Further studies to investigate the signaling mechanisms identified that ligation of CM1‑induced apoptosis in A549 cell involved FasL expression, caspase-8, ERK1/2 and Akt kinase, whereas apoptosis of HCC827 cells was induced through caspase-9, JNK and c-jun‑dependent pathways. Taken together, we suggest that CM1 could be developed as a therapeutic target of lung cancer regardless of EGFR mutation status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Carcinoma, Non-Small-Cell Lung
  • Cell Line, Tumor
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Germinal Center / cytology
  • Germinal Center / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mutation
  • Reactive Oxygen Species / metabolism

Substances

  • Antibodies, Monoclonal
  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • centrocyte centroblast marker 1 protein, human
  • EGFR protein, human
  • ErbB Receptors