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Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells

BACKGROUND: Myofibroblasts in the cancer microenvironment have recently been implicated in tumour growth and metastasis of gastric cancer. However, the mechanisms responsible for the regulation of myofibroblasts in cancer-associated fibroblasts (CAFs) remain unclear. This study was performed to clar...

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Autores principales: Fuyuhiro, Y, Yashiro, M, Noda, S, Kashiwagi, S, Matsuoka, J, Doi, Y, Kato, Y, Hasegawa, T, Sawada, T, Hirakawa, K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185946/
https://www.ncbi.nlm.nih.gov/pubmed/21863023
http://dx.doi.org/10.1038/bjc.2011.330
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author Fuyuhiro, Y
Yashiro, M
Noda, S
Kashiwagi, S
Matsuoka, J
Doi, Y
Kato, Y
Hasegawa, T
Sawada, T
Hirakawa, K
author_facet Fuyuhiro, Y
Yashiro, M
Noda, S
Kashiwagi, S
Matsuoka, J
Doi, Y
Kato, Y
Hasegawa, T
Sawada, T
Hirakawa, K
author_sort Fuyuhiro, Y
collection PubMed
description BACKGROUND: Myofibroblasts in the cancer microenvironment have recently been implicated in tumour growth and metastasis of gastric cancer. However, the mechanisms responsible for the regulation of myofibroblasts in cancer-associated fibroblasts (CAFs) remain unclear. This study was performed to clarify the mechanisms for regulation of myofibroblasts in gastric cancer microenvironment. METHODS: Two CAFs (CaF-29 and CaF-33) from the tumoural gastric wall and a normal fibroblast (NF-29) from the nontumoural gastric wall, 4 human gastric cancer cell lines from scirrhous gastric cancer (OCUM-2MD3 and OCUM-12), and non-scirrhous gastric cancer (MKN-45 and MKN-74) were used. Immunofluorescence microscopy by triple-immunofluorescence labelling (α-SMA, vimentin, and DAPI) was performed to determine the presence of α-SMA-positive myofibroblasts. Real-time RT–PCR was performed to examine α-SMA mRNA expression. RESULTS: Immunofluorescence microscopy showed that the frequency of myofibroblasts in CaF-29 was greater than that in NF-29. The number of myofibroblasts in gastric fibroblasts gradually decreased with serial passages. Transforming growth factor-β (TGF-β) significantly increased the α-SMA expression level of CAFs. Conditioned medium from OCUM-2MD3 or OCUM-12 cells upregulated the α-SMA expression level of CAFs, but that from MKN-45 or MKN-74 cells did not. The α-SMA upregulation effect of conditioned medium from OCUM-2MD3 or OCUM-12 cells was significantly decreased by an anti-TGF-β antibody or Smad2 siRNA. CONCLUSION: Transforming growth factor-β from scirrhous gastric carcinoma cells upregulates the number of myofibroblasts in CAFs.
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spelling pubmed-31859462012-09-27 Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells Fuyuhiro, Y Yashiro, M Noda, S Kashiwagi, S Matsuoka, J Doi, Y Kato, Y Hasegawa, T Sawada, T Hirakawa, K Br J Cancer Molecular Diagnostics BACKGROUND: Myofibroblasts in the cancer microenvironment have recently been implicated in tumour growth and metastasis of gastric cancer. However, the mechanisms responsible for the regulation of myofibroblasts in cancer-associated fibroblasts (CAFs) remain unclear. This study was performed to clarify the mechanisms for regulation of myofibroblasts in gastric cancer microenvironment. METHODS: Two CAFs (CaF-29 and CaF-33) from the tumoural gastric wall and a normal fibroblast (NF-29) from the nontumoural gastric wall, 4 human gastric cancer cell lines from scirrhous gastric cancer (OCUM-2MD3 and OCUM-12), and non-scirrhous gastric cancer (MKN-45 and MKN-74) were used. Immunofluorescence microscopy by triple-immunofluorescence labelling (α-SMA, vimentin, and DAPI) was performed to determine the presence of α-SMA-positive myofibroblasts. Real-time RT–PCR was performed to examine α-SMA mRNA expression. RESULTS: Immunofluorescence microscopy showed that the frequency of myofibroblasts in CaF-29 was greater than that in NF-29. The number of myofibroblasts in gastric fibroblasts gradually decreased with serial passages. Transforming growth factor-β (TGF-β) significantly increased the α-SMA expression level of CAFs. Conditioned medium from OCUM-2MD3 or OCUM-12 cells upregulated the α-SMA expression level of CAFs, but that from MKN-45 or MKN-74 cells did not. The α-SMA upregulation effect of conditioned medium from OCUM-2MD3 or OCUM-12 cells was significantly decreased by an anti-TGF-β antibody or Smad2 siRNA. CONCLUSION: Transforming growth factor-β from scirrhous gastric carcinoma cells upregulates the number of myofibroblasts in CAFs. Nature Publishing Group 2011-09-27 2011-08-23 /pmc/articles/PMC3185946/ /pubmed/21863023 http://dx.doi.org/10.1038/bjc.2011.330 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Fuyuhiro, Y
Yashiro, M
Noda, S
Kashiwagi, S
Matsuoka, J
Doi, Y
Kato, Y
Hasegawa, T
Sawada, T
Hirakawa, K
Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title_full Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title_fullStr Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title_full_unstemmed Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title_short Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells
title_sort upregulation of cancer-associated myofibroblasts by tgf-β from scirrhous gastric carcinoma cells
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185946/
https://www.ncbi.nlm.nih.gov/pubmed/21863023
http://dx.doi.org/10.1038/bjc.2011.330
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