RRC ID 74931
Author Fujita M, Ito-Fujita Y, Iyoda T, Sasada M, Okada Y, Ishibashi K, Osawa T, Kodama H, Fukai F, Suzuki H.
Title Peptide TNIIIA2 Derived from Tenascin-C Contributes to Malignant Progression in Colitis-Associated Colorectal Cancer via β1-Integrin Activation in Fibroblasts.
Journal Int J Mol Sci
Abstract 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.
Volume 20(11)
Published 2019-6-5
DOI 10.3390/ijms20112752
PII ijms20112752
PMID 31195598
PMC PMC6601010
MeSH Animals Azoxymethane Caco-2 Cells Cell Proliferation Colitis / complications* Colonic Polyps / pathology Colorectal Neoplasms / etiology* Colorectal Neoplasms / pathology* Culture Media, Conditioned / pharmacology Dextran Sulfate Disease Models, Animal Disease Progression* Epithelial Cells / metabolism Epithelial Cells / pathology Fibroblasts / metabolism* Fibroblasts / pathology Humans Integrin beta1 / metabolism* Male Mice, Inbred ICR Paracrine Communication Peptides / metabolism* Tenascin / metabolism*
IF 4.556
Human and Animal Cells WI-38(RCB0704)