title: Discovery of an uncovered region in fibrin clots and its clinical significance.
abstract: Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102-10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102-10 mAb was mapped to a hydrophobic region on the Bβ chain that interacted closely with a counterpart region on the γ chain in a soluble state. New anti-Bβ and anti-γ mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102-10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant.
authors.affiliation: Division of Developmental Therapeutics, Research Centre for Innovative Oncology, National Cancer Centre Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hisada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasunaga
authors.forename: Shingo
authors.initials: S
authors.lastname: Hanaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Saijou
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsuji
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.forename: Shino
authors.initials: S
authors.lastname: Manabe
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Kuroda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kuratsu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology*; D001665:Binding Sites; D001777:Blood Coagulation / Q000276:immunology*; D018604:Epitope Mapping / Q000379:methods*; D005337:Fibrin / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D000936:Antigen-Antibody Complex; D005337:Fibrin