title: Label-free quantitative proteomic analysis of benzo(a)pyrene-transformed 16HBE cells serum-free culture supernatant and xenografted nude mice sera.
abstract: To screen potential biomarkers of benzo(a)pyrene (BaP)-induced lung cancer, the proteomic profiles of BaP-transformed 16HBE cell line T-16HBE-C1 cells serum-free culture supernatant and xenografted nude mice sera were compared with those of 16HBE group by utilizing label-free quantitative proteomic strategy. By employing nano-LC-MS/MS technology followed by MaxQuant and Perseus processing, 489 differentially expressed proteins were identified between T-16HBE-C1 and 16HBE cells serum-free culture supernatant, and 49 significantly up-regulated proteins were identified in T-16HBE-C1 xenografted nude mice sera. Three proteins neuropilin-2 (NRP2), clusterin (CLU) and A-kinase anchor protein 12 (AKAP12) were up-regulated in the serum-free culture supernatant of T-16HBE-C1 cells. These 3 human proteins were present in the sera of nude mice xenografted with T-16HBE-C1 cells, but were undetectable in mice xenografted with 16HBE cells. The proteomic results of NRP2 and AKAP12 were confirmed by Western blotting and enzyme-linked immunosorbent assays, respectively. Moreover, the serum NRP2 levels were significantly elevated at the 4th day after tumor cell implantation and showed good positive correlation with tumor growth characterized by tumor volume. In conclusion, serum NRP2, CLU and AKAP12 could be potential biomarkers of BaP-induced lung cancer. The proteomic results will gain deeper insights into the mechanisms of BaP-induced carcinogenesis.
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China. Electronic address: zhaopeng@bjmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Juanling
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Yao
authors.affiliation: Medical and Healthy Analytical Center, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Yongrui
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing, 100191, PR China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Toxicology, Peking University Health Science Center, Beijing, 100191, PR China. Electronic address: zhouzc@bjmu.edu.cn.
authors.forename: Zongcan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D054758:A Kinase Anchor Proteins / Q000032:analysis / Q000097:blood; D000818:Animals; D001564:Benzo(a)pyrene; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D002461:Cell Line, Transformed; D051152:Clusterin / Q000032:analysis / Q000097:blood; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D039943:Neuropilin-2 / Q000032:analysis / Q000097:blood; D040901:Proteomics
chemical_list: D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; C486333:Akap1 protein, mouse; D014408:Biomarkers, Tumor; D051152:Clusterin; D039943:Neuropilin-2; D001564:Benzo(a)pyrene
keywords: AKAP12; Benzo(a)pyrene; CLU; Label-free quantitative proteomics; NRP2; T-16HBE-C1 cells