Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.

The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism...

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Autores principales:	Satoshi Takagi, Shigeo Sato, Tomoko Oh-hara, Miho Takami, Sumie Koike, Yuji Mishima, Kiyohiko Hatake, Naoya Fujita
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/371badaf6d0b449ca1ff7fa393a4d7f9
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spelling	oai:doaj.org-article:371badaf6d0b449ca1ff7fa393a4d7f92021-11-18T08:58:30ZPlatelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.1932-620310.1371/journal.pone.0073609https://doaj.org/article/371badaf6d0b449ca1ff7fa393a4d7f92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23991201/?tool=EBIhttps://doaj.org/toc/1932-6203The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis. Interestingly, the MS-1 monoclonal antibody attenuated the growth of Aggrus-positive tumors in vivo. Moreover, the humanized chimeric MS-1 antibody, ChMS-1, also exhibited strong antitumor activity against Aggrus-positive lung squamous cell carcinoma xenografted into NOD-SCID mice compromising antibody-dependent cellular cytotoxic and complement-dependent cytotoxic activities. Because Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth of the lung squamous cell carcinoma in vivo, Aggrus may be involved in not only tumor metastasis but also tumor growth by promoting platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Our results indicate that molecular target drugs inhibiting specific platelet-tumor interactions can be developed as antitumor drugs that suppress both metastasis and proliferation of tumors such as lung squamous cell carcinoma.Satoshi TakagiShigeo SatoTomoko Oh-haraMiho TakamiSumie KoikeYuji MishimaKiyohiko HatakeNaoya FujitaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e73609 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satoshi Takagi Shigeo Sato Tomoko Oh-hara Miho Takami Sumie Koike Yuji Mishima Kiyohiko Hatake Naoya Fujita Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
description	The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis. Interestingly, the MS-1 monoclonal antibody attenuated the growth of Aggrus-positive tumors in vivo. Moreover, the humanized chimeric MS-1 antibody, ChMS-1, also exhibited strong antitumor activity against Aggrus-positive lung squamous cell carcinoma xenografted into NOD-SCID mice compromising antibody-dependent cellular cytotoxic and complement-dependent cytotoxic activities. Because Aggrus knockdown suppressed platelet-induced proliferation in vitro and tumor growth of the lung squamous cell carcinoma in vivo, Aggrus may be involved in not only tumor metastasis but also tumor growth by promoting platelet-tumor interaction, platelet activation, and secretion of platelet-derived factors in vivo. Our results indicate that molecular target drugs inhibiting specific platelet-tumor interactions can be developed as antitumor drugs that suppress both metastasis and proliferation of tumors such as lung squamous cell carcinoma.
format	article
author	Satoshi Takagi Shigeo Sato Tomoko Oh-hara Miho Takami Sumie Koike Yuji Mishima Kiyohiko Hatake Naoya Fujita
author_facet	Satoshi Takagi Shigeo Sato Tomoko Oh-hara Miho Takami Sumie Koike Yuji Mishima Kiyohiko Hatake Naoya Fujita
author_sort	Satoshi Takagi
title	Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
title_short	Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
title_full	Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
title_fullStr	Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
title_full_unstemmed	Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.
title_sort	platelets promote tumor growth and metastasis via direct interaction between aggrus/podoplanin and clec-2.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/371badaf6d0b449ca1ff7fa393a4d7f9
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_version_	1718421073998905344

Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.

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