title: The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration.
abstract: The extracellular matrix (ECM) molecule tenascin C (TNC) is known to be highly expressed under various pathological conditions such as inflammation and cancer. It has been reported that the expression of TNC is correlated with the malignant potential of cancer. In our laboratory, it was found that the peptide derived from the alternative splicing domain A2 in TNC, termed TNIIIA2, has been shown to influence a variety of cellular processes, such as survival, proliferation, migration, and differentiation. In this study, we investigated the effect of TNC/TNIIIA2 on the invasion and metastasis of colon cancer cells, Colon26-M3.1, or PMF-Ko14, using an in vitro and in vivo experimental system. The degree of cell invasion was increased by the addition of TNC and TNIIIA2 in a dose-dependent manner. The invasion by TNC and TNIIIA2 were suppressed by an MMP inhibitor or TNIIIA2-blocking antibody. In an in vivo experiment, pulmonary metastasis was promoted conspicuously by the addition of TNIIIA2. In this study, we found that colon cancer cell invasion and metastasis was accelerated by TNC/TNIIIA2 via MMP induction. This result suggests the possibility of a new strategy targeting TNC/TNIIIA2 for colon cancer.
authors.affiliation: Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba Graduate School, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. hideoszk@md.tsukuba.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. ssdy1321.tus@gmail.com.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sasada
authors.affiliation: Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan. kamiyas@jiu.ac.jp.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Kamiya
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. yuka02079@gmail.com.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. hika.w.12v345key@gmail.com.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. bitawan850@gmail.com.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. k.ishibashi0604@gmail.com.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. iyoda@rs.tus.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iyoda
authors.affiliation: Department of Gastroenterology, Hitachi Medical Education and Research Center, Tsukuba University Hospital, 2-1-1 Jyounancho, Hitachi, Ibaraki 317-0077, Japan. ynk-aki@md.tsukuba.ac.jp.
authors.forename: Akinori
authors.initials: A
authors.lastname: Yanaka
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. fukai@rs.noda.tus.ac.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Fukai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D019063:Tenascin; D020782:Matrix Metalloproteinases
keywords: TNIIIA2; colon cancer; extracellular matrix; matrix metalloproteinase; tenascin C