Molecular Identification of Aggrus/T1α as a Platelet Aggregation-inducing Factor Expressed in Colorectal Tumors

Yukinari Kato, Naoya Fujita, Akiko Kunita, Shigeo Sato, Mika Kaneko, Motoki Osawa, Takashi Tsuruo

Research output: Contribution to journalArticlepeer-review

235 Citations (Scopus)

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 T1α/gp38P/ OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1α-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/T1α is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.

Original languageEnglish
Pages (from-to)51599-51605
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number51
DOIs
Publication statusPublished - 2003 Dec 19
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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