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人子宫肌瘤与基因表达谱分析:一种用于研究分泌型白细胞蛋白酶抑制剂介导的肿瘤侵袭的新型体外模型。

Human uterus myoma and gene expression profiling: A novel in vitro model for studying secretory leukocyte protease inhibitor-mediated tumor invasion.

作者信息

Mikami Yoshikazu, Fukushima Atsushi, Komiyama Yusuke, Iwase Takashi, Tsuda Hiromasa, Higuchi Yasuhiko, Hayakawa Satoshi, Kuyama Kayo, Komiyama Kazuo

机构信息

Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Microscopic Anatomy, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata 951-8122, Japan.

RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro, Tsurumi, Yokohama-shi, Kanagawa 230-0045, Japan.

出版信息

Cancer Lett. 2016 Aug 28;379(1):84-93. doi: 10.1016/j.canlet.2016.05.028. Epub 2016 May 26.

Abstract

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that diminishes tissue destruction during inflammation. A recent report revealed high levels of SLPI expression in the oral carcinoma cell. In addition, overexpression of SLPI up-regulates metastasis in lung carcinoma cells. On the other hand, matrix metalloproteinases (MMPs) are proteinases that participate in extracellular matrix degradation. SLPI and MMPs are involved as accelerators of the tumor invasion process; however, their exact roles are not fully understood. Understanding the mechanism of tumor invasion requires models that take the effect of microenvironmental factors into account. In one such in vitro model, different carcinoma cells have been shown to invade myoma tissue in highly distinct patterns. We have used this myoma model, as it provides a more natural stroma-like environment, to investigate the role of SLPI in tumor invasion. Our results indicate that the model provides a relevant matrix for tumor invasion studies, and that SLPI is important for the invasion of oral carcinoma Ca9-22 cells in conjunction with MMPs. Furthermore, using bioinformatics analysis, we have identified candidates as key molecules involved in SLPI-mediated tumor invasion.

摘要

分泌型白细胞蛋白酶抑制剂(SLPI)是一种丝氨酸蛋白酶抑制剂,可减少炎症期间的组织破坏。最近的一份报告显示口腔癌细胞中SLPI表达水平很高。此外,SLPI的过表达上调了肺癌细胞的转移。另一方面,基质金属蛋白酶(MMPs)是参与细胞外基质降解的蛋白酶。SLPI和MMPs作为肿瘤侵袭过程的促进因子参与其中;然而,它们的确切作用尚未完全了解。了解肿瘤侵袭机制需要考虑微环境因素影响的模型。在一个这样的体外模型中,已显示不同的癌细胞以高度不同的模式侵袭肌瘤组织。我们使用了这个肌瘤模型,因为它提供了更自然的基质样环境,来研究SLPI在肿瘤侵袭中的作用。我们的结果表明该模型为肿瘤侵袭研究提供了一个相关基质,并且SLPI与MMPs一起对口腔癌Ca9-22细胞的侵袭很重要。此外,通过生物信息学分析,我们已鉴定出作为参与SLPI介导的肿瘤侵袭的关键分子的候选物。

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