title: Conformational changes in inter-α-trypsin inhibitor heavy chain 4 activate its tumor-specific activity in mice with B16 melanoma.
abstract: It is known that blood serum proteins of tumor‑bearing mice display tumor‑specific activity. However, to date, the nature of this activity has remained elusive, and no tumor‑specific proteins have been detected in the blood serum of tumor‑bearing animals compared with those in healthy animals. The present study postulated and investigated the hypothesis that the observed tumor‑specific activity of the blood serum proteins is not associated with the appearance of novel serum proteins but with changes in the conformation of the existing ones. The present study showed conformational changes of two serum albumin proteins and inter‑α‑trypsin inhibitor heavy chain 4 (ITIH4) in mice with B16 melanoma compared to tumor‑free mice, as determined by differences in the products of proteolysis by proteomic analysis following column chromatography. The differences in the conformation of serum albumin in mice with B16 melanoma and tumor‑free mice were accompanied by a change in the interaction of these molecules with the fatty acid spin probe 16‑doxyl stearic acid. The differential conformation of ITIH4 in mice with B16 melanoma and that in tumor‑free mice was accompanied by inhibition of tumor growth and increased life span. Analysis of the role of protease‑anti‑proteases (serpins) in the serum of tumor‑bearing animals in tumor growth confirmed the hypothesis that tumor growth in the body is mediated, at least in part, via balancing of serpins.
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Natalya G
authors.initials: NG
authors.lastname: Kormosh
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Davidova
authors.affiliation: Research Institute for Physical‑Chemical Medicine, Moscow 119828, Russia.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Kopyltsov
authors.affiliation: Institute of Gene Biology, Russian Academy of Sciences, Moscow 117334, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Serebryakova
authors.affiliation: Kazakh Scientific Research Institute of Oncology and Radiobiology, Ministry of Health, Republic of Kazakhstan, Almaaty 480012, Kazakhstan.
authors.forename: Aigul O
authors.initials: AO
authors.lastname: Kabieva
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Konstantin E
authors.initials: KE
authors.lastname: Voyushin
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Suriya M
authors.initials: SM
authors.lastname: Sitdikova
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Berick S
authors.initials: BS
authors.lastname: Amandzholov
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Michail V
authors.initials: MV
authors.lastname: Kiselevskii
authors.affiliation: Laboratory of Cell Immunity, Institute of Diagnosis and Therapy, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
authors.forename: Fedor V
authors.initials: FV
authors.lastname: Donenko
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000737:chemistry; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011487:Protein Conformation; D053491:Proteinase Inhibitory Proteins, Secretory; D059748:Proteolysis; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; C112970:Itih4 protein, mouse; D053491:Proteinase Inhibitory Proteins, Secretory; D012709:Serum Albumin; D014357:Trypsin