Journal article
Tenascin-C, over expressed in lung cancer down regulates effector functions of tumor infiltrating lymphocytes
Lung cancer (Amsterdam, Netherlands), Vol.47(1), pp.17-29
2005
DOI: 10.1016/j.lungcan.2004.05.016
PMID: 15603851
Abstract
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.
Details
- Title: Subtitle
- Tenascin-C, over expressed in lung cancer down regulates effector functions of tumor infiltrating lymphocytes
- Creators
- Kalpaj Parekh - Washington University in St. LouisSabarinathan Ramachandran - Washington University in St. LouisJoel Cooper - Washington University in St. LouisDarell Bigner - Duke UniversityAlexander Patterson - Washington University in St. LouisT. Mohanakumar - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Lung cancer (Amsterdam, Netherlands), Vol.47(1), pp.17-29
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.lungcan.2004.05.016
- PMID
- 15603851
- ISSN
- 0169-5002
- eISSN
- 1872-8332
- Language
- English
- Date published
- 2005
- Academic Unit
- Anatomy and Cell Biology; Cardiothoracic Surgery
- Record Identifier
- 9984284335402771
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