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Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts

Inflammatory bowel diseases increase the risk of colorectal cancer and colitis-associated colorectal cancer (CAC). Tenascin-C, a matricellular protein, is highly expressed in inflammatory bowel diseases, especially colorectal cancer. However, the role of tenascin-C in the development of CAC is not y...

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Autores principales: Fujita, Motomichi, Ito-Fujita, Yuka, Iyoda, Takuya, Sasada, Manabu, Okada, Yuko, Ishibashi, Kazuma, Osawa, Takuro, Kodama, Hiroaki, Fukai, Fumio, Suzuki, Hideo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601010/
https://www.ncbi.nlm.nih.gov/pubmed/31195598
http://dx.doi.org/10.3390/ijms20112752
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author Fujita, Motomichi
Ito-Fujita, Yuka
Iyoda, Takuya
Sasada, Manabu
Okada, Yuko
Ishibashi, Kazuma
Osawa, Takuro
Kodama, Hiroaki
Fukai, Fumio
Suzuki, Hideo
author_facet Fujita, Motomichi
Ito-Fujita, Yuka
Iyoda, Takuya
Sasada, Manabu
Okada, Yuko
Ishibashi, Kazuma
Osawa, Takuro
Kodama, Hiroaki
Fukai, Fumio
Suzuki, Hideo
author_sort Fujita, Motomichi
collection PubMed
description Inflammatory bowel diseases increase the risk of colorectal cancer and colitis-associated colorectal cancer (CAC). Tenascin-C, a matricellular protein, is highly expressed in inflammatory bowel diseases, especially colorectal cancer. However, the role of tenascin-C in the development of CAC is not yet fully understood. We previously showed that a peptide derived from tenascin-C, peptide TNIIIA2, induces potent and sustained activation of β1-integrin. Moreover, we recently reported that peptide TNIIIA2 promotes invasion and metastasis in colon cancer cells. Here, we show the pathological relevance of TNIIIA2-related functional site for the development of CAC. First, expression of the TNIIIA2-containing TNC peptides/fragments was detected in dysplastic lesions of an azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. In vitro experiments demonstrated that conditioned medium from peptide TNIIIA2-stimulated human WI-38 fibroblasts induced malignant transformation in preneoplastic epithelial HaCaT cells. Indeed, these pro-proliferative effects stimulated by peptide TNIIIA2 were abrogated by peptide FNIII14, which has the ability to inactivate β1-integrin. Importantly, peptide FNIII14 was capable of suppressing polyp formation in the AOM/DSS model. Therefore, tenascin-C-derived peptide TNIIIA2 may contribute to the formation of CAC via activation of stromal fibroblasts based on β1-integrin activation. Peptide FNIII14 could represent a potential prophylactic treatment for CAC.
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spelling pubmed-66010102019-07-18 Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts Fujita, Motomichi Ito-Fujita, Yuka Iyoda, Takuya Sasada, Manabu Okada, Yuko Ishibashi, Kazuma Osawa, Takuro Kodama, Hiroaki Fukai, Fumio Suzuki, Hideo Int J Mol Sci Article Inflammatory bowel diseases increase the risk of colorectal cancer and colitis-associated colorectal cancer (CAC). Tenascin-C, a matricellular protein, is highly expressed in inflammatory bowel diseases, especially colorectal cancer. However, the role of tenascin-C in the development of CAC is not yet fully understood. We previously showed that a peptide derived from tenascin-C, peptide TNIIIA2, induces potent and sustained activation of β1-integrin. Moreover, we recently reported that peptide TNIIIA2 promotes invasion and metastasis in colon cancer cells. Here, we show the pathological relevance of TNIIIA2-related functional site for the development of CAC. First, expression of the TNIIIA2-containing TNC peptides/fragments was detected in dysplastic lesions of an azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. In vitro experiments demonstrated that conditioned medium from peptide TNIIIA2-stimulated human WI-38 fibroblasts induced malignant transformation in preneoplastic epithelial HaCaT cells. Indeed, these pro-proliferative effects stimulated by peptide TNIIIA2 were abrogated by peptide FNIII14, which has the ability to inactivate β1-integrin. Importantly, peptide FNIII14 was capable of suppressing polyp formation in the AOM/DSS model. Therefore, tenascin-C-derived peptide TNIIIA2 may contribute to the formation of CAC via activation of stromal fibroblasts based on β1-integrin activation. Peptide FNIII14 could represent a potential prophylactic treatment for CAC. MDPI 2019-06-05 /pmc/articles/PMC6601010/ /pubmed/31195598 http://dx.doi.org/10.3390/ijms20112752 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fujita, Motomichi
Ito-Fujita, Yuka
Iyoda, Takuya
Sasada, Manabu
Okada, Yuko
Ishibashi, Kazuma
Osawa, Takuro
Kodama, Hiroaki
Fukai, Fumio
Suzuki, Hideo
Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title_full Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title_fullStr Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title_full_unstemmed Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title_short Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts
title_sort peptide tniiia2 derived from tenascin-c contributes to malignant progression in colitis-associated colorectal cancer via β1-integrin activation in fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601010/
https://www.ncbi.nlm.nih.gov/pubmed/31195598
http://dx.doi.org/10.3390/ijms20112752
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