Host-derived MMP-13 exhibits a protective role in lung metastasis of melanoma cells by local endostatin production.
Host-derived MMP-13 exhibits a protective role in lung metastasis of melanoma cells by local endostatin production.
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DOI：
10.1038/bjc.2011.431
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发表时间：
2011-11-08
影响因子：
8.8
通讯作者：
Okada, Y.
中科院分区：
文献类型：
--
作者：
Fukuda, H.;Mochizuki, S.;Abe, H.;Okano, H. J.;Hara-Miyauchi, C.;Okano, H.;Yamaguchi, N.;Nakayama, M.;D'Armiento, J.;Okada, Y.
虽然基质金属蛋白酶（MMPs）与肿瘤发生和癌症进展有关，但MMP-13在黑色素瘤细胞转移中的作用知之甚少。在MMP-13敲除（KO）和野生型（WT）小鼠中分析静脉内注射后小鼠黑素瘤B16 BL 6细胞的肺转移。采用RT-PCR、real-time PCR、免疫印迹和免疫组化方法检测肺组织MMP-13的mRNA和蛋白表达。观察SDF-1α、CXCR 4和内皮抑素的表达，以及内皮抑素对体外培养的黑色素瘤细胞和肺转移瘤的影响。MMP-13 KO小鼠中B16 BL 6细胞的肺转移显著高于WT小鼠2.5-5.7倍。在静脉内注射黑素瘤细胞后第1天刺激WT小鼠肺组织中MMP-13的表达，并将MMP-13免疫定位于肺中的血管内皮细胞。WT小鼠肺组织中内皮抑素的形成（而非SDF-1α的降解）与肺转移减少相关。内皮抑素可显著抑制B16 BL 6细胞的单层损伤迁移，并显著抑制细胞的Matrigel侵袭和跨内皮侵袭。此外，MMP-13 KO小鼠中黑色素瘤细胞的肺转移通过腹膜内施用内皮抑制素而减少。我们的研究结果表明，MMP-13是过度生产的内皮细胞在肺与黑色素瘤细胞和肺转移的保护作用，通过局部生成内皮抑制素。
Although matrix metalloproteinases (MMPs) are implicated in tumourigenesis and cancer progression, the role of MMP-13 in melanoma cell metastases is poorly understood. Lung metastases of mouse melanoma B16BL6 cells were analysed in MMP-13 knockout (KO) and wild-type (WT) mice after intravenous injection. The mRNA and protein expression of MMP-13 in lung tissues was analysed by RT–PCR, real-time PCR, immunoblotting and immunohistochemistry. The expression of SDF-1α, CXCR4 and endostatin, and effects of endostatin to cultured melanoma cells and lung metastases were also studied. Lung metastases of B16BL6 cells were significantly higher by 2.5–5.7-fold in MMP-13 KO mice than in WT mice. The expression of MMP-13 in WT mouse lung tissue was stimulated on day 1 after intravenous injection of the melanoma cells and MMP-13 was immunolocalised to vascular endothelial cells in the lungs. Endostatin formation, but not degradation of SDF-1α, in the lung tissue was associated with reduced lung metastasis in WT mice. Endostatin significantly inhibited migration of B16BL6 cells in monolayer wounding assay and remarkably suppressed Matrigel invasion and transendothelial invasion of the cells. In addition, lung metastases of melanoma cells in MMP-13 KO mice were reduced by intraperitoneal administration of endostatin. Our results suggest that MMP-13 is overproduced by endothelial cells in the lungs with melanoma cells and has a protective role in lung metastasis by local generation of endostatin.
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影响因子：
6
作者：
Johansson, N;Vaalamo, M;Kähäri, VM
通讯作者：
Kähäri, VM
影响因子：
11.2
作者：
McCawley, LJ;Crawford, HC;Matrisian, LM
通讯作者：
Matrisian, LM
影响因子：
11.2
作者：
Acuff, Heath B.;Sinnamon, Mark;Matrisian, Lynn M.
通讯作者：
Matrisian, Lynn M.
影响因子：
11.2
作者：
Acuff, HB;Carter, KJ;Matrisian, LM
通讯作者：
Matrisian, LM
一组基因（包括WISP-1）的过表达，这是小鼠D122 Lewis Lung Carcinoma和B16-F10.9黑色素瘤细胞系共有的。
影响因子：
8.8
作者：
Margalit, O;Eisenbach, L;Amariglio, N;Kaminski, N;Harmelin, A;Pfeffer, R;Shohat, M;Rechavi, G;Berger, R
通讯作者：
Berger, R