Lung cancer is classified into small cell lung cancer and non-small cell lung cancer. Small cell lung cancer is a major cause of cancer deaths and accounts for 15 to 20% of all lung cancers. Because this cancer is initially highly responsive to chemotherapy, early detections are desired. Serum tumor markers are non-invasive diagnostic tools for malignant tumors and they are commonly used for the screening of cancer and as an indicator of the treatment effect. In this study, in order to develop new tumor marker for small cell lung cancer, secreted proteins from small cell lung carcinoma cell lines are analyzed in proteomic approach. Lung carcinoma cell lines were cultured in serum-free media and conditioned media were collected. Proteins fractioned with RP-HPLC were digested by protease and peptide sequence was determined using tandem mass spectrometry (MS/MS). About 50 proteins were detected in cultured media using MALDI-TOF MS/MS. Among these proteins, proneurotensin / neuromedin N (proNT/NMN) was determined in cultured medium. Moreover, proNT/NMN was detected in 4 of 9 small cell lung carcinoma cell lines but not from 9 non-small cell lung carcinoma cell lines. These results indicate proNT/NMN has a high potential as a specific tumor marker of small cell lung cancer. ProNT/NMN is the common precursor of the two related neuropeptides, neuromedin N (NMN) and neurotensin (NT). It is well known that neuroendocrine carcinomas (including small cell lung carcinomas) secrete various neuropeptides such as neurotensin or gastrin-releasing peptide. However, neuropeptides are known to be unstable in the blood and they are very difficult to establish as tumor markers. Because pro-form hormone, such as pro-gastrin releasing peptide (ProGRP), is more stable in the blood, it is likely that proNT/NMN has great potential as a tumor marker in a similar way to proGRP.
