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Am. J. Respir. Cell Mol. Biol., Vol 13, No. 3, Sep 1995, 271-278.

Expression of tumor necrosis factor receptors in human lung cancer cells and normal lung tissues

H Shimomoto, Y Hasegawa, Y Nozaki, N Takagi, T Shibagaki, A Nakao and K Shimokata
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.

The purpose of this study was to investigate the expression of tumor necrosis factor (TNF) receptors for the control of the biologic action of TNF-alpha in lung cancer cells and normal lung tissues. Lung cancer specimens and normal lung tissues were freshly obtained in pairs from 15 patients who underwent surgery for lung cancer. Thirteen lung cancer specimens expressed the 55 kDa TNF receptor messenger RNA (mRNA), whereas only six lung cancer specimens expressed the 75 kDa TNF receptor mRNA by Northern blot analysis. The 55 kDa and 75 kDa TNF receptors mRNA were detected in all and 11 normal lung tissues, respectively. All four lung carcinoma cell lines examined expressed the 55 kDa TNF receptor mRNA, but only RERF-LC-MS (MS) expressed both the 55 kDa and 75 kDa TNF receptors mRNA. Immunohistochemical examination revealed that lung cancer cells expressed the 55 kDa TNF receptor, but not the 75 kDa TNF receptor at the protein level. In normal lung tissues, the 55 kDa TNF receptor was detected in alveolar macrophages, bronchioles, and some small vessels. The 75 kDa TNF receptor was detected in alveolar macrophages. All four lung carcinoma cell lines examined exhibited the only 55 kDa TNF receptor. TNF-mediated tumor cell lysis was observed in all lung carcinoma cell lines that exhibited the 55 kDa TNF receptor except A549, which is a TNF-insensitive cell line. In surface binding assays, specific surface binding of TNF-alpha to TNF-insensitive cell line A549 was observed to be about half that of TNF-sensitive cell lines. We demonstrated the expression of two distinct TNF receptors in human lung cancer and normal lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


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