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2015 ; 2015
(ä): 974615
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Activating transcription factor 4 promotes angiogenesis of breast cancer through
enhanced macrophage recruitment
#MMPMID25883982
Liu C
; Li Z
; Wang L
; Tong L
; He N
; Chen Y
; Liu Y
; Wu Z
; Sun P
; Xiang R
; Ren G
; Su W
Biomed Res Int
2015[]; 2015
(ä): 974615
PMID25883982
show ga
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.