Effect of CXCL14 on Migration of Mds Via CXCL12/CXCR4 Axis in Vitro

Objective:To detect the expression level of chemokine CXCL-14 in patients with MDS, and to explore how it is regulated and what clinical effects may occour . For the further step ,to find new target in MDS therapy.Method:45 patients with MDS and 28 donors' peripheral blood samples were included. The expression of chemokine CXCL14, CXCL12 / CXCR4 and CXCR7 were detected by ELISA and FCM. Logistic regression analysis confirmed the association between chemokine expression level and disease progression. Kaplan-meier survival analysis ,introducing time factors, show how CXCL14 works on median survival time and cumulative survival. Methylation specific PCR detected the promoter methylation level in CXCL14.To affirm the clinical significaonce of CXCL14 in MDS, the group conduct experiment with cell line SKM-1 and rebuild the cell in the way of CXCL14 and CXCR7 overexpression .CCK-8 cell proliferation experiment tested cell vigor, Flow Cytometry detected cell apoptosis, transwell chemotactic experiment evaluated cell migration and invasion.Result:With the progression of MDS, the expression of receptors, CXCR4 and CXCR7, on tumor cell membrane increases .Statistical analysis showed that CXCL14 expression of stem cell mobilized donors was significantly high. Logistic regression analysis showed that increased expression of cxcl14 might hinder MDS progression, and overexpression of CXCL12 / CXCR4 axis was beneficial to disease progression. Kaplan-meier survival analysis showed that the median survival time and cumulative survival rate of patients with high CXCL14 expression were both better than the low CXCL14 expression group's. In the CXCL14 low-expression group, the gene promoter was hypermethylated.The expression of CXCR4 and CXCR7 on the surface of cell SKM-1 was down-regulated after Descitabine treatment, similarly in CXCL14 overexpression. In vitro, the high expression of CXCL14 could inhibit cell SKM-1 proliferation and promote cell apoptosis, and weak the cell migration and invasion induced by CXCL12/CXCR4 axis.Conclusion: In MDS, up-regulating CXCL14 expression might is one of the key factors to prevent the excessive activation of CXCL12 /CXCR4 axis, to maintain the stem cells in dynamic balance and limit the migration of tumor cells. To stimulate CXCL14 in vivo and infusion CXCL14 analogues are expected to be a new way in MDS treatment.