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Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer

BACKGROUND: The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediat...

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Autores principales: Windus, Louisa CE, Glover, Tristan T, Avery, Vicky M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850923/
https://www.ncbi.nlm.nih.gov/pubmed/24073816
http://dx.doi.org/10.1186/1476-4598-12-112
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author Windus, Louisa CE
Glover, Tristan T
Avery, Vicky M
author_facet Windus, Louisa CE
Glover, Tristan T
Avery, Vicky M
author_sort Windus, Louisa CE
collection PubMed
description BACKGROUND: The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediating tumour-stromal interactions. METHODS: Utilising 3D in vitro assays we evaluated and compared 1. Monocultures of prostate metastatic PC3, bone stromal derived HS5 and prostate epithelial RWPE-1 cells and 2. Tumour-stromal co-cultures (PC3 + HS5) to ascertain changes in cellular phenotype, function and expression of metastatic markers. RESULTS: In comparison to 3D monocultures of PC3 or HS5 cells, when cultured together, these cells displayed up-regulated invasive and proliferative qualities, along with altered expression of epithelial-to-mesenchymal and chemokine protein constituents implicated in metastatic dissemination. When co-cultured, HS5 cells were found to re-express N-Cadherin and chemokine receptor CXCR7. Alterations in N-Cadherin expression were found to be mediated by soluble factors secreted by PC3 tumour cells, while chemokine receptor re-expression was dependent on direct cell-cell interactions. We have also shown that integrins beta 1 and alpha 6 play an integral role in maintaining cell homeostasis and mediating expression of E-Cadherin, N-Cadherin and vimentin, in addition to chemokine receptor CXCR7. CONCLUSIONS: Collectively our results suggest that both PC3 and HS5 cells provide a “protective” and reciprocal milieu that promotes tumour growth. As such 3D co-cultures may serve as a more complex and valid biological model in the drug discovery pipeline.
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spelling pubmed-38509232013-12-05 Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer Windus, Louisa CE Glover, Tristan T Avery, Vicky M Mol Cancer Research BACKGROUND: The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediating tumour-stromal interactions. METHODS: Utilising 3D in vitro assays we evaluated and compared 1. Monocultures of prostate metastatic PC3, bone stromal derived HS5 and prostate epithelial RWPE-1 cells and 2. Tumour-stromal co-cultures (PC3 + HS5) to ascertain changes in cellular phenotype, function and expression of metastatic markers. RESULTS: In comparison to 3D monocultures of PC3 or HS5 cells, when cultured together, these cells displayed up-regulated invasive and proliferative qualities, along with altered expression of epithelial-to-mesenchymal and chemokine protein constituents implicated in metastatic dissemination. When co-cultured, HS5 cells were found to re-express N-Cadherin and chemokine receptor CXCR7. Alterations in N-Cadherin expression were found to be mediated by soluble factors secreted by PC3 tumour cells, while chemokine receptor re-expression was dependent on direct cell-cell interactions. We have also shown that integrins beta 1 and alpha 6 play an integral role in maintaining cell homeostasis and mediating expression of E-Cadherin, N-Cadherin and vimentin, in addition to chemokine receptor CXCR7. CONCLUSIONS: Collectively our results suggest that both PC3 and HS5 cells provide a “protective” and reciprocal milieu that promotes tumour growth. As such 3D co-cultures may serve as a more complex and valid biological model in the drug discovery pipeline. BioMed Central 2013-09-30 /pmc/articles/PMC3850923/ /pubmed/24073816 http://dx.doi.org/10.1186/1476-4598-12-112 Text en Copyright © 2013 Windus et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Windus, Louisa CE
Glover, Tristan T
Avery, Vicky M
Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title_full Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title_fullStr Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title_full_unstemmed Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title_short Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer
title_sort bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3d model of prostate cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850923/
https://www.ncbi.nlm.nih.gov/pubmed/24073816
http://dx.doi.org/10.1186/1476-4598-12-112
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