The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9

详细信息    查看全文

• 作者：Jiang Li ; Renhu Sun ; Kaixiong Tao ; Guobin Wang
• 关键词：Matrix metalloproteinase-9 ; CC chemokine receptor 7 ; Whole-body fluorescence imaging ; Colon cancer metastasis
• 刊名：Digestive and Liver Disease
• 出版年：2011
• 出版时间：January 2011
• 年：2011
• 卷：43
• 期：1
• 页码：40-47
• 全文大小：1441 K

文摘

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.