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源自腱生蛋白-C的细胞外基质肽TNIIIA2对结肠癌细胞浸润的促进作用

The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration.

作者信息

Suzuki Hideo, Sasada Manabu, Kamiya Sadahiro, Ito Yuka, Watanabe Hikaru, Okada Yuko, Ishibashi Kazuma, Iyoda Takuya, Yanaka Akinori, Fukai Fumio

机构信息

Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba Graduate School, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

出版信息

Int J Mol Sci. 2017 Jan 17;18(1):181. doi: 10.3390/ijms18010181.

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.

摘要

细胞外基质(ECM)分子腱生蛋白C(TNC)在诸如炎症和癌症等各种病理条件下高表达。据报道,TNC的表达与癌症的恶性潜能相关。在我们实验室,发现源自TNC中可变剪接结构域A2的肽,称为TNIIIA2,已被证明可影响多种细胞过程,如存活、增殖、迁移和分化。在本研究中,我们使用体外和体内实验系统研究了TNC/TNIIIA2对结肠癌细胞Colon26-M3.1或PMF-Ko14侵袭和转移的影响。通过以剂量依赖性方式添加TNC和TNIIIA2,细胞侵袭程度增加。TNC和TNIIIA2的侵袭被MMP抑制剂或TNIIIA2阻断抗体抑制。在体内实验中,添加TNIIIA2显著促进了肺转移。在本研究中,我们发现TNC/TNIIIA2通过诱导MMP加速了结肠癌细胞的侵袭和转移。这一结果提示了针对结肠癌靶向TNC/TNIIIA2的新策略的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2635/5297813/446999f9aa12/ijms-18-00181-g001.jpg

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