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Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture

A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-β...

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Autores principales: Nguyen, Hong T, Zhuang, Yan, Sun, Lichun, Kantrow, Steven P, Kolls, Jay K, You, Zongbing, Zhuo, Ying, Shan, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626791/
https://www.ncbi.nlm.nih.gov/pubmed/23409704
http://dx.doi.org/10.1186/1475-2867-13-16
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author Nguyen, Hong T
Zhuang, Yan
Sun, Lichun
Kantrow, Steven P
Kolls, Jay K
You, Zongbing
Zhuo, Ying
Shan, Bin
author_facet Nguyen, Hong T
Zhuang, Yan
Sun, Lichun
Kantrow, Steven P
Kolls, Jay K
You, Zongbing
Zhuo, Ying
Shan, Bin
author_sort Nguyen, Hong T
collection PubMed
description A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-β1 and type I collagen (Col-1) on lung adenocarcinoma cells. Similar to normal alveolar epithelial cells, the well-differentiated lung adenocarcinoma cells in rBM 3-D culture undergo acinar morphogeneis that features polarized epithelial cell spheres with a single central lumen. Either TGF-β1 or Col-1 modestly distorts acinar morphogenesis. On the other hand, TGF-β1 and Col-1 synergistically induce a transition from acinar morphology into stellate morphology that is characteristic of invasive and metastatic cancer cells. Inhibition of the Src kinase activity abrogates induction of stellate morphology, activation of Akt and mTOR, and the expression of tumor promoting genes by TGF-β1 and Col-1. To a similar extent, pharmacological inhibition of mTOR abrogates the cellular responses to TGF-β1 and Col-1. In summary, we demonstrate that TGF-β1 and Col-1 promote stellate morphogenesis of lung cancer cells. Our findings further suggest that the Src-Akt-mTOR axis mediates stellate morphogenesis. These findings also indicate that rBM 3-D culture can serve as an ideal platform for swift and cost-effective screening of therapeutic candidates at the interface of the tumor and its microenvironment.
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spelling pubmed-36267912013-04-16 Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture Nguyen, Hong T Zhuang, Yan Sun, Lichun Kantrow, Steven P Kolls, Jay K You, Zongbing Zhuo, Ying Shan, Bin Cancer Cell Int Primary Research A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-β1 and type I collagen (Col-1) on lung adenocarcinoma cells. Similar to normal alveolar epithelial cells, the well-differentiated lung adenocarcinoma cells in rBM 3-D culture undergo acinar morphogeneis that features polarized epithelial cell spheres with a single central lumen. Either TGF-β1 or Col-1 modestly distorts acinar morphogenesis. On the other hand, TGF-β1 and Col-1 synergistically induce a transition from acinar morphology into stellate morphology that is characteristic of invasive and metastatic cancer cells. Inhibition of the Src kinase activity abrogates induction of stellate morphology, activation of Akt and mTOR, and the expression of tumor promoting genes by TGF-β1 and Col-1. To a similar extent, pharmacological inhibition of mTOR abrogates the cellular responses to TGF-β1 and Col-1. In summary, we demonstrate that TGF-β1 and Col-1 promote stellate morphogenesis of lung cancer cells. Our findings further suggest that the Src-Akt-mTOR axis mediates stellate morphogenesis. These findings also indicate that rBM 3-D culture can serve as an ideal platform for swift and cost-effective screening of therapeutic candidates at the interface of the tumor and its microenvironment. BioMed Central 2013-02-14 /pmc/articles/PMC3626791/ /pubmed/23409704 http://dx.doi.org/10.1186/1475-2867-13-16 Text en Copyright © 2013 Nguyen 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 Primary Research
Nguyen, Hong T
Zhuang, Yan
Sun, Lichun
Kantrow, Steven P
Kolls, Jay K
You, Zongbing
Zhuo, Ying
Shan, Bin
Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title_full Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title_fullStr Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title_full_unstemmed Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title_short Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
title_sort src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626791/
https://www.ncbi.nlm.nih.gov/pubmed/23409704
http://dx.doi.org/10.1186/1475-2867-13-16
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