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


METHODS
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.


RESULTS
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.


CONCLUSIONS
MMP-9 and CCR7 may be useful targets for the treatment of lymphatic metastasis in colon cancer.
Li
Jiang
J
Union Hospital, Huazhong University of Science and Technology, Wuhan, PR China.
Sun
Renhu
R
Tao
Kaixiong
K
Wang
Guobin
G
D000818:Animals; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D054421:Chemokine CCL21; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D020780:Matrix Metalloproteinase 9