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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1730-1739. Prepublished online as a Blood First Edition Paper on June 9, 2008; DOI 10.1182/blood-2007-11-124693. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-124693v1 112/5/1730    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nakazawa, Y. Articles by Fujita, N. Search for Related Content PubMed PubMed Citation Articles by Nakazawa, Y. Articles by Fujita, N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis Youya Nakazawa1,2, Shigeo Sato1, Mikihiko Naito3, Yukinari Kato4, Kazuhiko Mishima5, Hiroyuki Arai2, Takashi Tsuruo1, and Naoya Fujita1 1 Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo; 2 Graduate School of Pharmaceutical Sciences and 3 Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo; 4 Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba; and 5 Saitama International Medical Center, Saitama Medical University, Saitama, Japan CD9 has been reported to play a role in tumor metastasis suppression. However, it is not fully understood how CD9 affects the hematogenous spread of tumor cells. To clarify a new mechanism (or mechanisms), we generated HT1080 cells that had been transfected with a CD9-expressing plasmid. Ectopic expression of CD9 in HT1080 cells actually reduced their metastatic ability. CD9 expression reduced lung retention and platelet ag-gregation activity of the transfectants. Because HT1080 cells express the metastasis-promoting, platelet aggregation-inducing factor Aggrus/podoplanin on their surface, we examined the relationship between CD9 and Aggrus. We discovered that CD9 formed a complex with Aggrus via transmembrane domains 1 and 2 (TM1 and TM2) of CD9. Investigation of the interaction revealed that each CD9 and Aggrus interacted homophilically, and that they colocalized in low-density membrane fractions. Deleting TM1 and TM2 attenuated the ability of CD9 to interact homophilically or to localize in low-density membrane fractions. The expression of CD9–wild-type (WT), but not CD9 lacking TM1 and TM2, attenuated the platelet aggregation and metastasis induced by forced expression of Aggrus in CHO cells. Therefore, CD9 may act as a metastasis suppressor, at least in part, by neutralizing Aggrus-mediated platelet aggregation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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