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肝素酶表达和细胞定位在口腔癌中的预后价值。

Prognostic value of heparanase expression and cellular localization in oral cancer.

机构信息

Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Post Office Box 9602, Haifa, Israel.

出版信息

Head Neck. 2011 Jun;33(6):871-7. doi: 10.1002/hed.21545. Epub 2010 Sep 21.

DOI:10.1002/hed.21545
PMID:20859999
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3010289/
Abstract

BACKGROUND

Metastases formation depends on the ability of tumor cells to invade basement membranes in a process involving enzymes capable of degrading extracellular matrix components.

METHODS

We examined the expression of heparanase in oral carcinomas and correlated its staining extent, intensity, and cellular localization with patients' outcome.

RESULTS

Quantitative real-time polymerase chain reaction (PCR) revealed over 4-fold increase in heparanase levels in oral carcinomas compared to adjacent normal tissue. Normal oral epithelium was found negative for heparanase, while all oral carcinomas stained positively for heparanase. Heparanase staining was associated with Ki67 staining, a measure of cell proliferation. Notably, whereas cytoplasmic localization of heparanase was associated with high-grade carcinomas, nuclear localization of the enzyme was found primarily in low-grade, well-differentiated tumors, and in all oral verrucous carcinomas.

CONCLUSION

Expression level and cellular localization of heparanase could serve as an important diagnostic marker in patients with oral cancer.

摘要

背景

转移的形成取决于肿瘤细胞侵袭基底膜的能力,这一过程涉及能够降解细胞外基质成分的酶。

方法

我们检测了口腔癌中肝素酶的表达,并将其染色程度、强度和细胞定位与患者的预后相关联。

结果

定量实时聚合酶链反应 (PCR) 显示,与相邻正常组织相比,口腔癌中肝素酶的水平增加了 4 倍以上。正常口腔上皮组织呈肝素酶阴性,而所有口腔癌均呈肝素酶阳性染色。肝素酶染色与 Ki67 染色相关,Ki67 是细胞增殖的一种衡量标准。值得注意的是,虽然细胞质中肝素酶的定位与高级别癌有关,但核内定位的酶主要存在于低级别、分化良好的肿瘤和所有口腔疣状癌中。

结论

肝素酶的表达水平和细胞定位可以作为口腔癌患者的重要诊断标志物。

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本文引用的文献

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PLoS One. 2009;4(4):e5181. doi: 10.1371/journal.pone.0005181. Epub 2009 Apr 10.
2
Heparanase regulates levels of syndecan-1 in the nucleus.乙酰肝素酶调节细胞核中Syndecan-1的水平。
PLoS One. 2009;4(3):e4947. doi: 10.1371/journal.pone.0004947. Epub 2009 Mar 23.
3
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Cancer Res. 2008 Dec 15;68(24):10077-85. doi: 10.1158/0008-5472.CAN-08-2910.
4
Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma.乙酰肝素酶对蛋白酶表达的刺激表明它是骨髓瘤侵袭性肿瘤表型的主要调节因子。
J Biol Chem. 2008 Nov 21;283(47):32628-36. doi: 10.1074/jbc.M806266200. Epub 2008 Sep 23.
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Heparanase induces VEGF C and facilitates tumor lymphangiogenesis.乙酰肝素酶诱导VEGF C并促进肿瘤淋巴管生成。
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