Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation

Abstract Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin t...

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Autores principales:	Kenichi Miyata, Ai Takemoto, Sakae Okumura, Makoto Nishio, Naoya Fujita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c32808f24e244388c9c730032f18191
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spelling	oai:doaj.org-article:0c32808f24e244388c9c730032f181912021-12-02T16:08:20ZPodoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation10.1038/s41598-017-04324-12045-2322https://doaj.org/article/0c32808f24e244388c9c730032f181912017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04324-1https://doaj.org/toc/2045-2322Abstract Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.Kenichi MiyataAi TakemotoSakae OkumuraMakoto NishioNaoya FujitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenichi Miyata Ai Takemoto Sakae Okumura Makoto Nishio Naoya Fujita Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
description	Abstract Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.
format	article
author	Kenichi Miyata Ai Takemoto Sakae Okumura Makoto Nishio Naoya Fujita
author_facet	Kenichi Miyata Ai Takemoto Sakae Okumura Makoto Nishio Naoya Fujita
author_sort	Kenichi Miyata
title	Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
title_short	Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
title_full	Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
title_fullStr	Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
title_full_unstemmed	Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
title_sort	podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0c32808f24e244388c9c730032f18191
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_version_	1718384513779761152

Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation

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