The CCL21/CCR7 pathway plays a key role in human colon cancer metastasis through regulation of matrix metalloproteinase-9
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.
aDepartment of Laparoscopic Surgery Unit, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China
bDepartment of Endoscopy Center, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, PR China
Corresponding author.
Corresponding 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.
ABSTRACT