Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.

The turnover of extracellular matrix liberates various cryptic molecules with novel biological activity. Among these are the collagen-derived anti-angiogenic fragments, some of which are suggested to affect carcinoma cells also directly. Arresten is an endogenous angiogenesis inhibitor that is deriv...

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Autores principales:	Mari Aikio, Ilkka Alahuhta, Sini Nurmenniemi, Juho Suojanen, Riitta Palovuori, Susanna Teppo, Timo Sorsa, Carlos López-Otín, Taina Pihlajaniemi, Tuula Salo, Ritva Heljasvaara, Pia Nyberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f467a4953a3e4f2481a4dce6dd3ce833
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spelling	oai:doaj.org-article:f467a4953a3e4f2481a4dce6dd3ce8332021-11-18T08:06:15ZArresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.1932-620310.1371/journal.pone.0051044https://doaj.org/article/f467a4953a3e4f2481a4dce6dd3ce8332012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227231/?tool=EBIhttps://doaj.org/toc/1932-6203The turnover of extracellular matrix liberates various cryptic molecules with novel biological activity. Among these are the collagen-derived anti-angiogenic fragments, some of which are suggested to affect carcinoma cells also directly. Arresten is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of the basement membrane collagen IV α1 chain. As the mere prevention of tumor angiogenesis leads to hypoxia that can result in selection of more aggressive cell types and reduces the efficacy of chemotherapy, we aimed here to elucidate how arresten influences the aggressive human carcinoma cells. Arresten efficiently inhibited migration and invasion of HSC-3 tongue carcinoma cells in culture and in an organotypic model. Subcutaneous Arr-HSC xenografts grew markedly more slowly in nude mice and showed reduced tumor cell proliferation, vessel density and local invasiveness. In the organotypic assay, HSC-3 cells overproducing arresten (Arr-HSC) showed induction of cell death. In monolayer culture the Arr-HSC cells grew in aggregated cobblestone-like clusters and, relative to the control cells, showed increased expression and localization of epithelial marker E-cadherin in cell-cell contacts. Application of electric cell-substrate impedance sensing (ECIS) further supported our observations on altered morphology and motility of the Arr-HSC cells. Administration of a function-blocking α1 integrin antibody abolished the impedance difference between the Arr-HSC and control cells suggesting that the effect of arresten on promotion of HSC-3 cell-cell contacts and cell spreading is at least partly mediated by α1β1 integrin. Collectively, our data suggest novel roles for arresten in the regulation of oral squamous carcinoma cell proliferation, survival, motility and invasion through the modulation of cell differentiation state and integrin signaling.Mari AikioIlkka AlahuhtaSini NurmenniemiJuho SuojanenRiitta PalovuoriSusanna TeppoTimo SorsaCarlos López-OtínTaina PihlajaniemiTuula SaloRitva HeljasvaaraPia NybergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51044 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mari Aikio Ilkka Alahuhta Sini Nurmenniemi Juho Suojanen Riitta Palovuori Susanna Teppo Timo Sorsa Carlos López-Otín Taina Pihlajaniemi Tuula Salo Ritva Heljasvaara Pia Nyberg Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
description	The turnover of extracellular matrix liberates various cryptic molecules with novel biological activity. Among these are the collagen-derived anti-angiogenic fragments, some of which are suggested to affect carcinoma cells also directly. Arresten is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of the basement membrane collagen IV α1 chain. As the mere prevention of tumor angiogenesis leads to hypoxia that can result in selection of more aggressive cell types and reduces the efficacy of chemotherapy, we aimed here to elucidate how arresten influences the aggressive human carcinoma cells. Arresten efficiently inhibited migration and invasion of HSC-3 tongue carcinoma cells in culture and in an organotypic model. Subcutaneous Arr-HSC xenografts grew markedly more slowly in nude mice and showed reduced tumor cell proliferation, vessel density and local invasiveness. In the organotypic assay, HSC-3 cells overproducing arresten (Arr-HSC) showed induction of cell death. In monolayer culture the Arr-HSC cells grew in aggregated cobblestone-like clusters and, relative to the control cells, showed increased expression and localization of epithelial marker E-cadherin in cell-cell contacts. Application of electric cell-substrate impedance sensing (ECIS) further supported our observations on altered morphology and motility of the Arr-HSC cells. Administration of a function-blocking α1 integrin antibody abolished the impedance difference between the Arr-HSC and control cells suggesting that the effect of arresten on promotion of HSC-3 cell-cell contacts and cell spreading is at least partly mediated by α1β1 integrin. Collectively, our data suggest novel roles for arresten in the regulation of oral squamous carcinoma cell proliferation, survival, motility and invasion through the modulation of cell differentiation state and integrin signaling.
format	article
author	Mari Aikio Ilkka Alahuhta Sini Nurmenniemi Juho Suojanen Riitta Palovuori Susanna Teppo Timo Sorsa Carlos López-Otín Taina Pihlajaniemi Tuula Salo Ritva Heljasvaara Pia Nyberg
author_facet	Mari Aikio Ilkka Alahuhta Sini Nurmenniemi Juho Suojanen Riitta Palovuori Susanna Teppo Timo Sorsa Carlos López-Otín Taina Pihlajaniemi Tuula Salo Ritva Heljasvaara Pia Nyberg
author_sort	Mari Aikio
title	Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
title_short	Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
title_full	Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
title_fullStr	Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
title_full_unstemmed	Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
title_sort	arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f467a4953a3e4f2481a4dce6dd3ce833
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Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.

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