Tenascin-C, over expressed in lung cancer down regulates effector functions of tumor infiltrating lymphocytes.

Published

Journal Article

PURPOSE: Extracellular matrix (ECM) proteins play a significant role in the survival and metastasis of cancer cells. Tenascin-C (TN-C) is an extracellular matrix protein and its large isoform has been implicated in tumor progression. Goal of this study was to analyze the expression of the small and large isoforms of TN-C in non-small cell lung cancer (NSCLC) and determine its functional significance. EXPERIMENTAL DESIGN: TN-C expression was studied in tumor and non-tumor tissue of patients with NSCLC at the mRNA and protein level. Immunomodulatory properties of the large isoform of TN-C were analyzed by determining its effect on lymphocyte proliferation and cytokine secretion by tumor-infiltrating lymphocytes (TIL). RESULTS: Quantitative real-time PCR analysis showed an eight-fold increase in the amount of large isoform in cancer cells compared to adjacent normal tissue. Expression at the protein level by Western blot analysis using a murine monoclonal anti-TN-C antibody detected increased expression of the large isoform in the tumor tissue that was correlated with the development of recurrent disease. A 18-fold increase in the expression of the large TN-C isoform was observed in patients with recurrent NSCLC compared to non-recurrent NSCLC. Large isoform of TN-C significantly inhibited anti-CD3 and mitogen-induced proliferation of human peripheral blood lymphocytes and interferon-gamma production by TIL isolated from the lung cancer specimens. CONCLUSIONS: Increased expression of TN-C observed at the site of tumor in NSCLC correlates with recurrence. TN-C inhibits TIL proliferation and cytokine thereby may promote tumor immune evasion and recurrence.

Full Text

Duke Authors

Cited Authors

  • Parekh, K; Ramachandran, S; Cooper, J; Bigner, D; Patterson, A; Mohanakumar, T

Published Date

  • January 2005

Published In

Volume / Issue

  • 47 / 1

Start / End Page

  • 17 - 29

PubMed ID

  • 15603851

Pubmed Central ID

  • 15603851

International Standard Serial Number (ISSN)

  • 0169-5002

Digital Object Identifier (DOI)

  • 10.1016/j.lungcan.2004.05.016

Language

  • eng

Conference Location

  • Ireland