Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain.
To identify potential markers associated with non-small cell lung cancer (NSCLC) metastasis to brain, comparative proteome analysis on two lung squamous cell carcinoma (SCC) cell lines, NCI-H226 and H226Br (the brain metastatic cell line of NCI-H226), was performed using two-dimensional electrophoresis (2-DE) followed by a tandem mass spectrometer with a matrix-assisted laser desorption/ionization (MALDI) source. Twenty differential proteins were identified, of which 6 proteins were up-regulated in H226Br cell compared with NCI-H226 cells, whereas 14 proteins were down-regulated. S100A7 and 14-3-3sigma, two of candidate proteins significantly upregulated and downregulated in H226Br cell, were selected to verify the liability of the differential proteins by Western blot. The results were in accordance with 2-D data. To determine whether S100A7 overexpression is actually associated with SCC metastasis to brain, S100A7 protein was testified in 10 brain metastasis tissues from NSCLC, 38 primary NSCLC tissues including half matched local positive lymph nodes, 5 primary brain tumors and 2 non-cancer brain tissues by immunohistochemistry. Of particular interest to us was that the positive staining of S100A7 could be found in 3/5 (60%) brain metastases tissue from SCC and 8/21 (38%) the primary lung SCC tissues, while no positive staining was observed in the brain metastases tissue from Ad (n=5), the primary adenocarcinoma (Ad) tissues (n=17), the primary brain tumors (n=5), all local positive lymph nodes from the primary NSCLC (n=19) and non-cancer brain tissues (n=2). These findings suggest that S100A7 expression is closely associated with SCC metastasis to brain and may be a potential biomarker for monitoring the development of SCC.
Zhang
Hao
H
Key Laboratory for Cell Proliferation and Regulation Biology Ministry of Education, Beijing Normal University, 19th Xinjiekouwai St., 100875 Beijing, China.
Wang
Yinping
Y
Chen
Yue
Y
Sun
Suozhu
S
Li
Na
N
Lv
Dongxia
D
Liu
Chuanjun
C
Huang
Lingyun
L
He
Dacheng
D
Xiao
Xueyuan
X
D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000175:diagnosis / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D010449:Peptide Mapping; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins
D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D020543:Proteome; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human