Experimental Study On Bone Marrow-derived Myeloid Progenitor Cells For Metastatic Recurrence Of Hepatocellular Carcinoma

Objective:To make use of bone marrow-derived myeloid progenitor cells' role on the process of angiogenesis,investigate the expression of tumor-associated macrophage in hepatocellular carcinoma(HCC) and clinicopathological characteristics.Methods:BALB/c nu/nu mice irradiated with 8 Gy were transplanted with bone marrow-derived cells from the same kind mouse.After 4 weeks when marrow reconstitution time finished transplated tumor in mice liver,and observe bone marrow cells' effect on angiogenesis during tumor growth.The expression of tumorassociated macrophages(TAMs),microvessel density(MVD) and vascular endothelial growth factor(VEGF) in tissues of 49 patients with hepatocellular carcinoma(HCC) were detected by immunohistochemisty SP method and automated image analysis quantification.Results:Here modified immunomagnetic methods using magnetic beads conjugated with anti-CD45 antibody were used to isolate bone marrow-derived myeloid progenitor cells from HCC xenografts;the MPCs presented typical appearance.Bone marrow-derived MPCs with stems cell marker CD133+reach to the top when 3 to 5 weeks after HCC xenografts.The quantitation of TAMs was strongly correlated with tumor vascular invasion(P＜0.05),and it was significantly associated with Edmonson classification pathologic histology cell differentiation(P＜0.01),no significant difference was found in patients' sex,age,HBsAg,AFP level and tumor diameter(P＞0.05).The expression of TAMs and MVD in hepatocellular carcinoma (HCC) were significantly positively correlated(r=0.56,P＜0.05),so were the expression of TAMs and VEGF(r=0.58,P＜0.05),and the expression of VEGF and MVD(r=0.334,P＜0.01)Conclusions:1.The overall level of engraftment is satisfactory in transplanted male BALB/c nu/nu mouse with 8.0 Gy irradiation.Bone marrow can be reconstituted completely after 4 weeks in transplanted mouse undergoing 8.0 Gy irradiation.2.Tumor angiogenesis reach to the top when 3 to 5 weeks after HCC xenografts and bone marrow reconstitution.MPCs can participate HCC tube angiogenesis,hasten the growth of HCC.3.TAMs were expressed in HCC at different levels and its expression level has significant correlation with tumor vascular invasion,which suggests TAMs may be one of the factors mediating tumor vascular invasion of HCC.4.The quantitation of TAMs was significantly associated with pathologic histology cell differentiation;it was strongly correlated with tumor vascular invasion and Edmonson classification.5.The expression of TAMS is significant difference in nomal tissue,intratumor and peritumor,intratumoral TAMS express highest.There was a positive correlation between the expression of TAMs and MVD in HCC,which suggested that TAMs may participate in the angiogenesis of HCC,and that represent a new pathway for angiogenesis of HCC and a new target for anti angiogenesis therapy of HCC.