Web Release Date: February 7,
Cathepsin D Is Secreted from M-BE Cells: Its Potential Role as a Biomarker of Lung Cancer

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Division of Proteomics, Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101318, P. R. China, Department of Etiology and Carcinogenesis, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P. R. China, Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing 100034, P. R. China, Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P. R. China, and Graduate School of Chinese Academy of Sciences, Beijing 100049, P. R. China
Received August 20, 2006

Abstract:
The early diagnosis of lung cancer is an effective approach to reduce the mortality caused by malignancy.
To explore serum biomarkers of lung cancer at early stage, M-BE, a SV40T-transformed human bronchial
epithelial cell line with the phenotypic features of early tumorigenesis at high passage, was cultured in
the conditioned media to collect its secretory proteins. The proteins secreted from different passage
M-BE cells were extracted and then separated by two-dimensional electrophoresis (2-DE). MALDI-TOF/TOF mass spectrometry was adopted to identify the passage-dependent 2-DE spots. Totally, 47 proteins
were identified, including 23 that were up-regulated and 24 that were down-regulated. Of these proteins,
cathepsin D was a typical secretory protein that exhibited the increased abundance either in culture
media or in cells during passaging. Furthermore, the proteomic conclusions were validated in the clinical
samples of lung cancer patients. When sandwich ELISA was used, the concentrations of cathepsin D
in plasma showed significant differences between lung squamous cell carcinomas (SCC, 104 cases)
and normal donors (36 cases, p
0.015). When tissue microarray (TMA) was used, cathepsin D
expression levels in SCC tissues (178 cases) were significantly higher than those in normal donors (40
cases, p < 0.001). The present study has revealed that M-BE cells at different passages could secrete
or release some proteins into the living environment, which might serve as the potential resource for
exploring the biomarkers of lung cancer.
Keywords: lung cancer
conditioned media
secretory protein
Cathepsin D
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