Angiogenesis plays an important role in the progression of tumor. Besides being 
regulated by tumor cells per se, tumor angiogenesis is also influenced by 
stromal cells in tumor microenvironment (TME), for example, tumor associated 
macrophages (TAMs). Activating transcription factor 4 (ATF4), a member of the 
ATF/CREB family, has been reported to be related to tumor angiogenesis. In this 
study, we found that exogenous overexpression of ATF4 in mouse breast cancer 
cells promotes tumor growth via increasing tumor microvascular density. However, 
ATF4 overexpression failed to increase the expression level of a series of 
proangiogenic factors including vascular endothelial growth factor A (VEGFA) in 
tumor cells in this model. Thus, we further investigated the infiltration of 
proangiogenic macrophages in tumor tissues and found that ATF4-overexpressing 
tumors could recruit more macrophages via secretion of macrophage colony 
stimulating factor (M-CSF). Overall, we concluded that exogenous overexpression 
of ATF4 in breast cancer cells may facilitate the recruitment of macrophages 
into tumor tissues and promote tumor angiogenesis and tumor growth indirectly.