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基质金属蛋白酶-2(MMP2)在结直肠癌进展中的作用:与临床病理特征的相关性及对细胞过程的影响

The Role of Matrix Metalloproteinase-2 (MMP2) in Colorectal Cancer Progression: Correlation With Clinicopathological Features and Impact on Cellular Processes.

作者信息

Ibraheem Qais

机构信息

Department of Anatomy, Biology and Histology, College of Medicine, University of Duhok, Duhok, IRQ.

出版信息

Cureus. 2024 Jun 8;16(6):e61941. doi: 10.7759/cureus.61941. eCollection 2024 Jun.

DOI:10.7759/cureus.61941
PMID:38978899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11229389/
Abstract

Background Colorectal cancer (CRC) is a prevalent and deadly disease characterized by significant molecular complexity. Matrix metalloproteinase-2 (MMP2) has been implicated in cancer progression due to its role in extracellular matrix degradation, yet comprehensive studies linking MMP2 expression to CRC progression and its molecular mechanisms remain needed. Methodology This study involved 90 CRC patients, with tumor and adjacent normal tissues analyzed via immunohistochemistry (IHC) to assess MMP2 expression. The human CRC cell line SW480 was treated with an MMP2 inhibitor, ARP100, and evaluated for changes in cell migration, invasion, proliferation, and apoptosis using various assays, including MTT, wound-healing, transwell, caspase activity, and western blot analysis. Results High MMP2 expression was significantly associated with advanced tumor stages, lymph node involvement, and metastasis in CRC patients. Compared to normal tissues, MMP2 expression was markedly higher in cancerous tissues. Inhibition of MMP2 in SW480 cells resulted in reduced migration, invasion, and proliferation, and induced apoptosis, evidenced by increased caspase 3 and 9 activities and higher levels of cleaved caspase proteins. Conclusion Elevated MMP2 expression is correlated with advanced CRC and aggressive tumor characteristics. MMP2 inhibition can suppress CRC cell invasiveness, migration, and proliferation while promoting apoptosis, suggesting its potential as a therapeutic target in CRC treatment.

摘要

背景

结直肠癌(CRC)是一种常见且致命的疾病,其特征是具有显著的分子复杂性。基质金属蛋白酶-2(MMP2)因其在细胞外基质降解中的作用而与癌症进展有关,但仍需要全面研究将MMP2表达与CRC进展及其分子机制联系起来。

方法

本研究纳入了90例CRC患者,通过免疫组织化学(IHC)分析肿瘤组织和相邻正常组织以评估MMP2表达。用MMP2抑制剂ARP100处理人CRC细胞系SW480,并使用各种检测方法,包括MTT、伤口愈合、Transwell、半胱天冬酶活性和蛋白质印迹分析,评估细胞迁移、侵袭、增殖和凋亡的变化。

结果

CRC患者中高MMP2表达与肿瘤晚期、淋巴结受累和转移显著相关。与正常组织相比,癌组织中MMP2表达明显更高。SW480细胞中MMP2的抑制导致迁移、侵袭和增殖减少,并诱导凋亡,半胱天冬酶3和9活性增加以及裂解的半胱天冬酶蛋白水平升高证明了这一点。

结论

MMP2表达升高与晚期CRC和侵袭性肿瘤特征相关。MMP2抑制可抑制CRC细胞的侵袭性、迁移和增殖,同时促进凋亡,表明其作为CRC治疗中治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/1bb56fc0138c/cureus-0016-00000061941-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/e786c1a7564b/cureus-0016-00000061941-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/674c9083890d/cureus-0016-00000061941-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/0c9602a21f02/cureus-0016-00000061941-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/1bb56fc0138c/cureus-0016-00000061941-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/e786c1a7564b/cureus-0016-00000061941-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/674c9083890d/cureus-0016-00000061941-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/0c9602a21f02/cureus-0016-00000061941-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9327/11229389/1bb56fc0138c/cureus-0016-00000061941-i04.jpg

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本文引用的文献

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Cancer Cell Int. 2023 Feb 14;23(1):26. doi: 10.1186/s12935-023-02862-5.
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Insights Into the Role of Matrix Metalloproteinases in Cancer and its Various Therapeutic Aspects: A Review.
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Front Mol Biosci. 2022 Sep 29;9:896099. doi: 10.3389/fmolb.2022.896099. eCollection 2022.
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Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis.肿瘤MMP2和MMP9过表达在乳腺癌中的预后价值:一项系统评价和荟萃分析。
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The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma.MMP-2 和 MMP-9 在下咽癌转移和发展中的作用。
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