[Effect of stromal cell-derived factor-1 and its receptor CXCR4 on liver metastasis of human colon cancer].
OBJECTIVE
To investigate the effect of chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 on liver metastasis of human colon cancer.


METHODS
Expression of CXCR4 in different colon cancer cell lines and SDF-1 in different tissues were detected by using Western-blot technique. Effect of SDF-1 and anti-CXCR4 monoclonal antibody (McAb) on proliferation and migration of HT-29 cells were measured using MTT methods. Model mimicking liver metastasis of human colon cancer was established by injecting HT-29 cells intrasplenically into BALB/C nude mice. Mice were randomly divided into AMD3100 treated group and control group. Liver metastatic rate and tumor foci were measured 7 weeks after.


RESULTS
HT-29 cells expressed higher level of CXCR4 protein, and liver tissue expressed higher level of SDF-1 protein. Compared with the control, SDF-1 could significantly induced the proliferation and migration of the HT-29 cells, and anti-CXCR4 McAb could inhibited both functions of SDF-1. The liver metastasis rate in the control group was 100%, and it was 40% in the AMD3100 treating group (P < 0.05). The mean liver metastasis number also significantly decreased by AMD3100 (7.8 +/- 2.6 vs 22.4 +/- 8.6, P < 0.05).


CONCLUSIONS
SDF-1/CXCR4 biological axis play an important role in liver metastasis of human colon cancer. Arrest of CXCR4 can inhibit liver metastasis of colon cancer through blocking cell proliferation and migration induced by SDF-1.
Ding
Yin-Lu
YL
Department of General Surgery, Second Hospital of Shandong University, Jinan 250033, China.
Fu
Qin-Ye
QY
Tang
Si-Feng
SF
Zhang
Jian-Liang
JL
Li
Zhan-Yuan
ZY
Li
Zhao-Ting
ZT
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism* / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019718:Receptors, CXCR4 / Q000378:metabolism* / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4