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人结肠癌中的核心蛋白聚糖:体内定位及对体外癌细胞行为的影响

Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

作者信息

Nyman Marie C, Sainio Annele O, Pennanen Mirka M, Lund Riikka J, Vuorikoski Sanna, Sundström Jari T T, Järveläinen Hannu T

机构信息

Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland (MCN, AOS, MMP, HTJ)

Turku Centre for Biotechnology , University of Turku, Turku, Finland(RJL, SV)

出版信息

J Histochem Cytochem. 2015 Sep;63(9):710-20. doi: 10.1369/0022155415590830. Epub 2015 May 22.

Abstract

Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational.

摘要

核心蛋白聚糖通常被认为是一种肿瘤抑制分子。然而,尽管已表明核心蛋白聚糖在恶性组织中存在差异表达,但除了非恶性基质细胞外,癌细胞是否也表达该分子往往仍不明确。在此,我们首先使用两个公开可用的数据库来分析关于正常和恶性人类结直肠组织样本中核心蛋白聚糖表达和免疫反应性的现有信息。分析表明,核心蛋白聚糖的表达和免疫反应性在人类结直肠组织的癌细胞中可能有所不同。因此,我们接下来使用核心蛋白聚糖的原位杂交和免疫组织化学更详细地检测了正常、癌前和恶性人类结直肠组织中核心蛋白聚糖的表达。我们的结果始终表明,人类结直肠癌组织中的恶性细胞既没有核心蛋白聚糖mRNA也没有免疫反应性。人类结肠神经内分泌肿瘤细胞也得到了相同的结果。使用逆转录定量聚合酶链反应(RT-qPCR),我们表明人类结肠癌细胞系也是核心蛋白聚糖阴性,这与上述体内结果一致。最后,我们证明核心蛋白聚糖转导人类结肠癌细胞系会导致其集落形成能力显著降低。因此,开发基于核心蛋白聚糖的人类结直肠恶性肿瘤辅助治疗策略是非常合理的。

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