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基质金属蛋白酶-8、转化生长因子-β1和血管内皮生长因子-C之间的相互作用共同促进了口腔舌鳞状细胞癌的侵袭性。

The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma.

作者信息

Åström Pirjo, Juurikka Krista, Hadler-Olsen Elin S, Svineng Gunbjørg, Cervigne Nilva K, Coletta Ricardo D, Risteli Juha, Kauppila Joonas H, Skarp Sini, Kuttner Samuel, Oteiza Ana, Sutinen Meeri, Salo Tuula

机构信息

Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Oulu 90014, Finland.

Medical Research Center Oulu, Oulu 90220, Finland.

出版信息

Br J Cancer. 2017 Sep 26;117(7):1007-1016. doi: 10.1038/bjc.2017.249. Epub 2017 Aug 3.

DOI:10.1038/bjc.2017.249
PMID:28772283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5625665/
Abstract

BACKGROUND

Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC).

METHODS

MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples.

RESULTS

MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-β1 (TGF-β1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-β1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells.

CONCLUSIONS

The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-β1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.

摘要

背景

基质金属蛋白酶-8（MMP-8）在多种癌症中具有抑癌特性。我们试图评估MMP-8在口腔舌鳞状细胞癌（OTSCC）中的功能。

方法

使用过表达MMP-8的OTSCC细胞来研究MMP-8对增殖、凋亡、迁移、侵袭以及基因和蛋白质表达的影响。此外，在原位小鼠舌癌模型中以及通过对患者样本进行免疫组织化学来评估MMP-8的功能。

结果

MMP-8减少了OTSCC细胞的侵袭和迁移，并降低了MMP-1、组织蛋白酶-K和血管内皮生长因子-C（VEGF-C）的表达。在对照细胞中，VEGF-C由转化生长因子-β1（TGF-β1）诱导产生，但在过表达MMP-8的细胞中则不然。在人类OTSCC样本中，低水平的MMP-8与高水平的VEGF-C相结合是癌症特异性生存率低的独立预测因素。TGF-β1处理也将过表达MMP-8的细胞的迁移恢复到对照细胞的水平。在小鼠舌癌中，MMP-8并未抑制转移，可能是因为它在外周癌细胞中被清除。

结论

MMP-8在OTSCC中的抑制作用可能是通过干扰TGF-β1和VEGF-C的功能以及改变蛋白酶表达来介导的。总之，低水平的MMP-8和高水平的VEGF-C表达在OTSCC中具有强大的独立预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/a2380f45aee0/bjc2017249f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/1e8ace913b2d/bjc2017249f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/30727866739d/bjc2017249f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/ca7088380769/bjc2017249f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/2099ceb24cf5/bjc2017249f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/a2380f45aee0/bjc2017249f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/1e8ace913b2d/bjc2017249f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/30727866739d/bjc2017249f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/ca7088380769/bjc2017249f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/2099ceb24cf5/bjc2017249f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58eb/5625665/a2380f45aee0/bjc2017249f5.jpg

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