title: The novel fusion protein sTRAIL-TMTP1 exhibits a targeted inhibition of primary tumors and metastases.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill tumor cells and enhance therapy in vivo. However, concerns regarding its considerable liver toxicity limit its use in humans as a cancer therapy. Tumor molecular targeted peptide 1 (TMTP1) has previously been reported by our laboratory to target primary tumors and metastatic foci. Here, we report a novel recombinant fusion protein, sTRAIL-TMTP1, which not only induced apoptosis in cancer cells in vitro but also inhibited tumor growth and metastases in vivo. Moreover, sTRAIL-TMTP1 impacted tumor angiogenesis. The biodistribution results demonstrated that sTRAIL-TMTP1 accumulation peaked 6 h after injection and persisted for 24 h in the tumor, while faint sTRAIL-TMTP1 accumulation was detected in normal organs in tumor-bearing mice. Thus, combining sTRAIL with TMTP1 resulted in high anti-tumor activity and low toxicity. In conclusion, the novel fusion protein sTRAIL-TMTP1 was successfully developed in our laboratory and was observed to induce apoptosis both in primary and metastatic cancer, which may lead to the development of novel, targeted anticancer agents.
  
  
  CONCLUSIONS
  Construction, purification, and characterization of the novel recombinant fusion protein, sTRAIL-TMTP1. sTRAIL-TMTP1 not only induce apoptosis in cancer cells but inhibit tumor growth and metastasis. sTRAIL-TMTP1 showed an impact on caspase activity and tumor angiogenesis. sTRAIL-TMTP1's accumulate in tumor with little accumulation in normal organs.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Liu
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Ma
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Yandong
authors.initials: Y
authors.lastname: Xi
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.forename: Wanhua
authors.initials: W
authors.lastname: Yang
authors.forename: Danfeng
authors.initials: D
authors.lastname: Luo
authors.forename: Liangsheng
authors.initials: L
authors.lastname: Fan
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Xi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C531959:asparagyl-valyl-valyl-arginyl-glutamine