title: Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors.
abstract: Platelets play an important role in hemostasis, thrombosis, and antimicrobial host defense and are also involved in the induction of inflammation, tissue repair, and tumor metastasis. We have previously characterized the platelet aggregation-inducing sialoglycoprotein (Aggrus/gp44) overexpressed on the surface of tumor cells. Because a platelet aggregation-neutralizing 8F11 monoclonal antibody that could specifically recognize Aggrus suppressed tumor-induced platelet aggregation, we have previously purified Aggrus by 8F11-affinity chromatography and found that purified Aggrus possessed the ability to induce aggregation of platelets. Here we show that Aggrus is identical to the T1alpha/gp38P/OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1alpha-2/gp36) induced platelet aggregation without requiring plasma components. Using the 8F11 antibody, we identified the highly conserved platelet aggregation-stimulating domain with putative O-glycosylated threonine residues as the critical determinant for exhibiting platelet aggregation-inducing capabilities. We compared the expression level of human aggrus mRNA using an array containing 160 cDNA pair samples derived from multiple human tumorigenic and corresponding normal tissues from individual patients. We found that expression level of aggrus was enhanced in most colorectal tumor patients. To confirm the protein expression, we generated anti-human Aggrus polyclonal antibodies. Immunohistochemical analysis revealed that Aggrus expression was frequently up-regulated in colorectal tumors. These results suggest that Aggrus/T1alpha is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.forename: Shigeo
authors.initials: S
authors.lastname: Sato
authors.forename: Mika
authors.initials: M
authors.lastname: Kaneko
authors.forename: Motoki
authors.initials: M
authors.lastname: Osawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
mesh_terms: D000818:Animals; D000906:Antibodies; D001665:Binding Sites; D001685:Biological Factors; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D017124:Conserved Sequence; D020869:Gene Expression Profiling; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D010974:Platelet Aggregation; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D000098853:Podoplanin
chemical_list: D000906:Antibodies; D001685:Biological Factors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C117468:PDPN protein, human