Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.

We have previously shown that fibroblast expression of α11β1 integrin stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand the molecular mechanisms whereby a collagen receptor on fibroblast can regulate tumor growth we have used a 3D heterospheroid system composed of A549...

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Autores principales:	Ning Lu, Tine V Karlsen, Rolf K Reed, Marion Kusche-Gullberg, Donald Gullberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/632e2e8cd8644a30a8b8ef68a460e8b4
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spelling	oai:doaj.org-article:632e2e8cd8644a30a8b8ef68a460e8b42021-11-25T06:06:39ZFibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.1932-620310.1371/journal.pone.0103173https://doaj.org/article/632e2e8cd8644a30a8b8ef68a460e8b42014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25076207/?tool=EBIhttps://doaj.org/toc/1932-6203We have previously shown that fibroblast expression of α11β1 integrin stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand the molecular mechanisms whereby a collagen receptor on fibroblast can regulate tumor growth we have used a 3D heterospheroid system composed of A549 tumor cells and fibroblasts without (α11+/+) or with a deletion (α11-/-) in integrin α11 gene. Our data show that α11-/-/A549 spheroids are larger than α11+/+/A549 spheroids, and that A549 cell number, cell migration and cell invasion in a collagen I gel are decreased in α11-/-/A549 spheroids. Gene expression profiling of differentially expressed genes in fibroblast/A549 spheroids identified CXCL5 as one molecule down-regulated in A549 cells in the absence of α11 on the fibroblasts. Blocking CXCL5 function with the CXCR2 inhibitor SB225002 reduced cell proliferation and cell migration of A549 cells within spheroids, demonstrating that the fibroblast integrin α11β1 in a 3D heterospheroid context affects carcinoma cell growth and invasion by stimulating autocrine secretion of CXCL5. We furthermore suggest that fibroblast α11β1 in fibroblast/A549 spheroids regulates interstitial fluid pressure by compacting the collagen matrix, in turn implying a role for stromal collagen receptors in regulating tensional hemostasis in tumors. In summary, blocking stromal α11β1 integrin function might thus be a stroma-targeted therapeutic strategy to increase the efficacy of chemotherapy.Ning LuTine V KarlsenRolf K ReedMarion Kusche-GullbergDonald GullbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e103173 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ning Lu Tine V Karlsen Rolf K Reed Marion Kusche-Gullberg Donald Gullberg Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
description	We have previously shown that fibroblast expression of α11β1 integrin stimulates A549 carcinoma cell growth in a xenograft tumor model. To understand the molecular mechanisms whereby a collagen receptor on fibroblast can regulate tumor growth we have used a 3D heterospheroid system composed of A549 tumor cells and fibroblasts without (α11+/+) or with a deletion (α11-/-) in integrin α11 gene. Our data show that α11-/-/A549 spheroids are larger than α11+/+/A549 spheroids, and that A549 cell number, cell migration and cell invasion in a collagen I gel are decreased in α11-/-/A549 spheroids. Gene expression profiling of differentially expressed genes in fibroblast/A549 spheroids identified CXCL5 as one molecule down-regulated in A549 cells in the absence of α11 on the fibroblasts. Blocking CXCL5 function with the CXCR2 inhibitor SB225002 reduced cell proliferation and cell migration of A549 cells within spheroids, demonstrating that the fibroblast integrin α11β1 in a 3D heterospheroid context affects carcinoma cell growth and invasion by stimulating autocrine secretion of CXCL5. We furthermore suggest that fibroblast α11β1 in fibroblast/A549 spheroids regulates interstitial fluid pressure by compacting the collagen matrix, in turn implying a role for stromal collagen receptors in regulating tensional hemostasis in tumors. In summary, blocking stromal α11β1 integrin function might thus be a stroma-targeted therapeutic strategy to increase the efficacy of chemotherapy.
format	article
author	Ning Lu Tine V Karlsen Rolf K Reed Marion Kusche-Gullberg Donald Gullberg
author_facet	Ning Lu Tine V Karlsen Rolf K Reed Marion Kusche-Gullberg Donald Gullberg
author_sort	Ning Lu
title	Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
title_short	Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
title_full	Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
title_fullStr	Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
title_full_unstemmed	Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.
title_sort	fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/a549 carcinoma heterospheroids.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/632e2e8cd8644a30a8b8ef68a460e8b4
work_keys_str_mv	AT ninglu fibroblasta11b1integrinregulatestensionalhomeostasisinfibroblasta549carcinomaheterospheroids AT tinevkarlsen fibroblasta11b1integrinregulatestensionalhomeostasisinfibroblasta549carcinomaheterospheroids AT rolfkreed fibroblasta11b1integrinregulatestensionalhomeostasisinfibroblasta549carcinomaheterospheroids AT marionkuschegullberg fibroblasta11b1integrinregulatestensionalhomeostasisinfibroblasta549carcinomaheterospheroids AT donaldgullberg fibroblasta11b1integrinregulatestensionalhomeostasisinfibroblasta549carcinomaheterospheroids
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Fibroblast α11β1 integrin regulates tensional homeostasis in fibroblast/A549 carcinoma heterospheroids.

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