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J. Biol. Chem., Vol. 278, Issue 51, 51599-51605, December 19, 2003

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Molecular Identification of Aggrus/T1 as a Platelet Aggregation-inducing Factor Expressed in Colorectal Tumors^*

Yukinari Kato¶, Naoya Fujita¶, Akiko Kunita, Shigeo Sato||, Mika Kaneko, Motoki Osawa, and Takashi Tsuruo||**

From the Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan, Department of Experimental and Forensic Pathology, Yamagata University School of Medicine, Yamagata 990-9585, Japan, and ^||Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan

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 T1/gp38P/OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1-2/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/T1 is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.

Received for publication, September 8, 2003 , and in revised form, October 1, 2003.

^* This study was supported in part by a special grant for Advanced Research on Cancer from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Both authors contributed equally to this work.

^** To whom correspondence should be addressed. Tel.: +81-3-5841-7861; Fax: +81-3-5841-8487; E-mail: ttsuruo{at}iam.u-tokyo.ac.jp.

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