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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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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. |
format | Online Article Text |
id | pubmed-3626791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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