Cathepsin D is secreted from M-BE cells: its potential role as a biomarker of lung cancer.
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 <or= 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.
Lou
Xiaomin
X
Division of Proteomics, Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101318, P. R. China.
Xiao
Ting
T
Zhao
Kang
K
Wang
Hao
H
Zheng
Hongwei
H
Lin
Dongmei
D
Lu
Youyong
Y
Gao
Yanning
Y
Cheng
Shujun
S
Liu
Siqi
S
Xu
Ningzhi
N
D014408:Biomarkers, Tumor / Q000097:blood; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002402:Cathepsin D / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D002402:Cathepsin D