Dig Liver Dis
2011 Jan;43(1):40-7.
doi: 10.1016/j.dld.2010.05.013. Epub 2010 Jul 6.
The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9
Jiang Li 1, Renhu Sun, Kaixiong Tao, Guobin Wang
Affiliations expand
PMID: 20609636
DOI: 10.1016/j.dld.2010.05.013
Abstract
Purpose: CC chemokine receptor 7 (CCR7) and matrix metalloproteinase-9 (MMP-9) have been associated with lymph node metastasis in human colon cancer. Studies have suggested a potential link between CCR7 and MMP-9 in cancer; however, the molecular mechanism by which C-C ligand 21/CCR7 promotes tumour dissemination in human colon cancer is not well understood. Thus, we aimed to determine whether MMP-9 is regulated by the C-C ligand 21/CCR7 in human colon cancer.
Method: RNA interference technology was employed to detect effect of CCR7 deficiency on the expression of MMP-9 in SW480 human colon cancer cells. We also evaluated the ability of CCR7 short hairpin RNA to inhibit MMP-9 production and tumour invasion in a xenografted mouse model by using whole-body fluorescence imaging and gelatin zymography.
Result: We found that CCR7 short hairpin RNA significantly inhibited C-C ligand 21/CCR7-induced up-regulation of MMP-9 in SW480 cells. Furthermore, knockdown of CCR7 significantly limited the production of MMP-9 and colon cancer metastasis in a xenografted mouse model. Mice that received SW480/control cells had progressively enlarging tumours and more lymphatic metastases, and these animals did not survive as long as mice that received SW480/CCR7⁻ cells.
Conclusion: MMP-9 and CCR7 may be useful targets for the treatment of lymphatic metastasis in colon cancer.
参考连接：
https://pubpeer.com/publications/B6181883505864FEC6A84A7477FD30
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