Journal Home
Search for

Articles in Press

Return to articles in press list

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

Jiang Lia, Renhu SunbCorresponding Author Informationemail address, Kaixiong Taoa, Guobin WangaCorresponding Author Informationemail address

Received 3 December 2009; accepted 20 May 2010. published online 08 July 2010.
Corrected Proof

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.

a Department of Laparoscopic Surgery Unit, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China

b Department of Endoscopy Center, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, PR China

Corresponding Author InformationCorresponding author.

Corresponding Author InformationCorresponding author at: Department of Laparoscopic Surgery Unit, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, PR China. Tel.: +86 27 85726301.

PII: S1590-8658(10)00195-7

doi:10.1016/j.dld.2010.05.013