Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model.
Nasopharyngeal carcinoma (NPC) is commonly diagnosed late due to its deep location and vague symptoms. To identify biomarkers for early NPC diagnosis, secreted proteomes of two NPC cell lines were analyzed. Proteins in the NPC cell-line cultured media were systematically identified by SDS-PAGE combined with MALDI-TOF MS. Twenty-three proteins were found in cultured media from both NPC cell lines. Among them, fibronectin, Mac-2 binding protein (Mac-2 BP), and plasminogen activator inhibitor 1 (PAI-1) were further confirmed by Western blot analysis. These three proteins were highly expressed in NPC biopsies, but weakly or not expressed in normal nasopharyngeal tissues. The serum levels of the three proteins were significantly higher in NPC patients (n = 46) than in normal controls (n = 47) (p < 0.01). NPC nude mice model (n = 9) also showed elevated levels of serum Mac-2 BP and PAI-1 compared with tumor-free mice (n = 9) (p < 0.01). Systematic analysis of cancer cell-secreted proteomes combined with animal tumor models can be a feasible, convenient strategy for searching multiple potential tumor markers. Furthermore, our work shows that fibronectin, Mac-2 BP, and PAI-1 may be potential markers for diagnosis of NPC.
Wu
Chih-Ching
CC
Department of Cell and Molecular Biology, Chang Gung University, Tao-Yuan, Taiwan, Republic of China.
Chien
Kun-Yi
KY
Tsang
Ngan-Ming
NM
Chang
Kai-Ping
KP
Hao
Sheng-Po
SP
Tsao
Chuang-Hui
CH
Chang
Yu-Sun
YS
Yu
Jau-Song
JS
D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D005353:Fibronectins; D037502:Galectin 3; D017395:Plasminogen Activator Inhibitor 1