Infiltration And Mechanism Of M2 Macrophage In Breast Cancer By Endoglin Of Vascular Endothelial Cells

ObjectiveTo study the alteration of M2 macrophages infiltration in the tumour in anti-angiogenic therapy targeting endoglin on vascular endothelial cells for breast cancer.MethodsEndoglin conditionally inducible-knockout(Eng-iKO)mouse model with in situ breast cancer were used as the object.Tumor tissues were harvested at 7th and 14 th day after engraftment at which time the growth difference between groups was significant during tumour progression.Markers expression of angiogenesis(CD31),endoglin(CD105),TAM(F4/80)and M2 macrophages(CD206),as well as IL-6 and IL-10 expression,and IL-6/janus kinase 2(JAK2)/signal transducer and activators of transcription 3(STAT3)proteins were all evaluated in tumour tissues of Eng-iKOe and control mice to explore the change of macrophages in tumours and its mechanism.ResultsWe found that tumour angiogenesis and growth were both inhibited in endoglin knockout group relative to the control group at day 7.This effect was gradually weakened over time as tumours progressed.No significant between-group difference was observed at day 14.On day 7 after engraftment,tumour angiogenesis and the amount of M2 macrophages were significantly decreased in breast cancer tissue;however,on day 14,the density of blood vessels and the amount of M2 macrophages were significantly increased in breast cancer tissue.A significantly positive correlation between the IL-6 level and the amount of M2 macrophages in breast cancer was found(P = 0.000,r = 0.952).No significant correlation was observed between the IL-10 level and the amount of M2 macrophages.The levels of IL-6,p-JAK2,and p-STAT3 in tumours were significantly lower on day 7 and were significantly higher on day 14 in the Eng-iKO group compared to the control group.No significant inter-group differences were observed in the level of JAK2 or STAT3 on day 7 and day 14.ConclusionAnti-angiogenic therapy targeting endoglin on vascular endothelial cells affected the infiltration of M2 macrophages in the tumour by modulating the IL-6 level.IL-6 levels in tumour tissues may be used to predict tumour immunity after anti-angiogenic therapy and to screen populations for anti-angiogenic therapy...