Effects of SDF-1 and CXCR4 on HPA Expression in Liver Metastases Induced by Colorectal Cancer Cells

Objective To study the effects of stromal cell derived factor 1 (SDF-1) on the expression of heparanase (HPA) of colorectal Lovo cells highly expressing chemotactic factor receptor CXCR4，and to explore the effects of SDF-1/CXCR4 on the expression of HPA in colorectal liver metastasic model in nude mice. Methods Colorectal Lovo cells were treated respectively with SDF-1 and AMD3100, an antagonist of SDF-1/CXCR4. The expression of HPA was detected by RT-PCR and immunocytochemical. Colorectal liver metastases model in nude mice was established. The expression of HPA protein of metastatic tumor cells treated or untreated with AMD3100 was detected respectively in liver metastases model. Results (1) The expressions of HPA mRNA increased gradually in colorectal Lovo cells treated with different concentrations of SDF-1(50 ng/ml, 100 ng/ml, 200 ng/ml). When treated with the same concentration of SDF-1 at different duration time, 12 and 24 hours,HPA expression increased gradually with the prolonged treating time. When the cells were treated with different concentrations of SDF-1(50 ng/ml, 100 ng/ml, 200 ng/ml) at the same duration time, HPA expression increased gradually with the increasing SDF-1 concentrations. (2) The mRNA and protein expression of HPA in SDF-1 treated group was higher than that in control group or the group treated with SDF-1 and AMD3100. (3) The expression of HPA of liver metastatic tumor cells decreased with the increasing of AMD3100. Conclusion (1) The expression of HPA of colorectal Lovo cells is able to be induced by SDF-1 in a concentration- or time-dependent manner. (2) AMD3100 could inhibit HPA expression stimulated by SDF-1 and may inhibit tumor metastasis.