From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

Abstract Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remain...

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Autores principales:	J. Plou, Y. Juste-Lanas, V. Olivares, C. del Amo, C. Borau, J. M. García-Aznar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa5cd0428bdd47f99c989fb173635ff0
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spelling	oai:doaj.org-article:aa5cd0428bdd47f99c989fb173635ff02021-12-02T15:06:28ZFrom individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β10.1038/s41598-018-30683-42045-2322https://doaj.org/article/aa5cd0428bdd47f99c989fb173635ff02018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30683-4https://doaj.org/toc/2045-2322Abstract Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-β regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-β in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-β induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-β activity.J. PlouY. Juste-LanasV. OlivaresC. del AmoC. BorauJ. M. García-AznarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. Plou Y. Juste-Lanas V. Olivares C. del Amo C. Borau J. M. García-Aznar From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
description	Abstract Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-β regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-β in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-β induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-β activity.
format	article
author	J. Plou Y. Juste-Lanas V. Olivares C. del Amo C. Borau J. M. García-Aznar
author_facet	J. Plou Y. Juste-Lanas V. Olivares C. del Amo C. Borau J. M. García-Aznar
author_sort	J. Plou
title	From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
title_short	From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
title_full	From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
title_fullStr	From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
title_full_unstemmed	From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β
title_sort	from individual to collective 3d cancer dissemination: roles of collagen concentration and tgf-β
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/aa5cd0428bdd47f99c989fb173635ff0
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From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β

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