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Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer

We evaluated the influence of the cancer microenvironment formed by peritoneal invasion (CMPI) on clinical findings in colon cancer patients. In addition to the association with poor prognosis, we discovered a relationship with bowel obstruction. Detailed analysis revealed that clinical findings rel...

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Autores principales: Yokota, Mitsuru, Kojima, Motohiro, Higuchi, Youichi, Nishizawa, Yuji, Kobayashi, Akihiro, Ito, Masaaki, Saito, Norio, Ochiai, Atsushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409892/
https://www.ncbi.nlm.nih.gov/pubmed/25613547
http://dx.doi.org/10.1111/cas.12615
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author Yokota, Mitsuru
Kojima, Motohiro
Higuchi, Youichi
Nishizawa, Yuji
Kobayashi, Akihiro
Ito, Masaaki
Saito, Norio
Ochiai, Atsushi
author_facet Yokota, Mitsuru
Kojima, Motohiro
Higuchi, Youichi
Nishizawa, Yuji
Kobayashi, Akihiro
Ito, Masaaki
Saito, Norio
Ochiai, Atsushi
author_sort Yokota, Mitsuru
collection PubMed
description We evaluated the influence of the cancer microenvironment formed by peritoneal invasion (CMPI) on clinical findings in colon cancer patients. In addition to the association with poor prognosis, we discovered a relationship with bowel obstruction. Detailed analysis revealed that clinical findings related to bowel obstruction occurred more frequently in patients with an elevated type tumor, which had peritoneal elastic laminal elevation to the tumor surface, compared to those with non-elevated type tumors among those with elastic laminal invasion (ELI). Lateral tumor spread and increase of tumor annularity rate in ELI-positive elevated type cases suggested the morphological progression from ELI-positive non-elevated type to elevated type. In addition, α-smooth muscle actin expression was the highest in ELI-positive elevated type, and prominent expressions were found not only in the deep tumor area but also in the shallow tumor area. Furthermore, contraction assays revealed the robust contractile ability of subperitoneal fibroblasts stimulated by cancer cell-conditioned medium. Our findings suggest that CMPI spread into the luminal side of the colonic wall along with tumor progression, which caused bowel obstruction through the activation of subperitoneal fibroblasts. However, although the clinical outcome was not different between the two types, the clinical findings were affected by the spread of CMPI. We are the first to explore how the alteration of the tumor-promoting microenvironment, along with tumor progression, contributes to the development of clinical findings.
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spelling pubmed-44098922015-10-05 Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer Yokota, Mitsuru Kojima, Motohiro Higuchi, Youichi Nishizawa, Yuji Kobayashi, Akihiro Ito, Masaaki Saito, Norio Ochiai, Atsushi Cancer Sci Original Articles We evaluated the influence of the cancer microenvironment formed by peritoneal invasion (CMPI) on clinical findings in colon cancer patients. In addition to the association with poor prognosis, we discovered a relationship with bowel obstruction. Detailed analysis revealed that clinical findings related to bowel obstruction occurred more frequently in patients with an elevated type tumor, which had peritoneal elastic laminal elevation to the tumor surface, compared to those with non-elevated type tumors among those with elastic laminal invasion (ELI). Lateral tumor spread and increase of tumor annularity rate in ELI-positive elevated type cases suggested the morphological progression from ELI-positive non-elevated type to elevated type. In addition, α-smooth muscle actin expression was the highest in ELI-positive elevated type, and prominent expressions were found not only in the deep tumor area but also in the shallow tumor area. Furthermore, contraction assays revealed the robust contractile ability of subperitoneal fibroblasts stimulated by cancer cell-conditioned medium. Our findings suggest that CMPI spread into the luminal side of the colonic wall along with tumor progression, which caused bowel obstruction through the activation of subperitoneal fibroblasts. However, although the clinical outcome was not different between the two types, the clinical findings were affected by the spread of CMPI. We are the first to explore how the alteration of the tumor-promoting microenvironment, along with tumor progression, contributes to the development of clinical findings. BlackWell Publishing Ltd 2015-04 2015-03-19 /pmc/articles/PMC4409892/ /pubmed/25613547 http://dx.doi.org/10.1111/cas.12615 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Yokota, Mitsuru
Kojima, Motohiro
Higuchi, Youichi
Nishizawa, Yuji
Kobayashi, Akihiro
Ito, Masaaki
Saito, Norio
Ochiai, Atsushi
Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title_full Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title_fullStr Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title_full_unstemmed Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title_short Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
title_sort spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409892/
https://www.ncbi.nlm.nih.gov/pubmed/25613547
http://dx.doi.org/10.1111/cas.12615
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