title: Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1α-VEGF signaling axis.
abstract: A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Previously, we have shown that GV1001 interacts with heat shock proteins (HSPs) and penetrates cell membranes to be localized in the cytoplasm. In this study, we have found that GV1001 lowered the level of intracellular and surface HSPs of various cancer cells. In hypoxic conditions, GV1001 treatment of cancer cells resulted in decreases of HSP90, HSP70, and HIF-1α. Subsequently, proliferation of cancer cells and synthesis of VEGF were significantly reduced by treatment using GV1001 in hypoxic conditions. In an experiment using a nude mouse xenograft model, GV1001 exerted a similar tumor suppressive effect, further confirming its anti-tumor efficacy. Higher apoptotic cell death, reduced proliferation of cells, and fewer blood vessels were observed in GV1001-treated tumors compared to control. In addition, significant reduction of Tie2+ CD11b+ monocytes, which were recruited by VEGF from tumor cells and play a critical role in angiogenesis, was observed in GV1001-treated tumors. Collectively, the results suggest that GV1001 possesses potential therapeutic efficacy in addition to its ability to induce anti-cancer immune responses by suppressing both HSP70 and HSP90.
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Bu-Kyung
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Seoung-Ae
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Byoung-Jun
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Yu-Sub
authors.initials: YS
authors.lastname: Won
authors.affiliation: Department of Conservative Dentistry, Dental Research Institute and School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Shon
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: innks@khu.ac.kr.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Cancer Research Institute and SNUMRC, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. Electronic address: kbumjoon@snu.ac.kr.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D042787:Receptor, TIE-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; C514987:GV1001 peptide; D019098:Telomerase
keywords: Cancer; Heat shock protein 70; Heat shock protein 90; Peptide; Telomerase