血管生成
癌症研究
肿瘤微环境
间质细胞
新生血管
血管内皮生长因子
血管内皮生长因子A
肿瘤进展
生物
癌症
医学
内科学
血管内皮生长因子受体
肿瘤细胞
作者
Chen Liu,Zongjin Li,Lina Wang,Lingling Tong,Ningning He,Yanan Chen,Yanhua Liu,Zhongjun Wu,Peiqing Sun,Rong Xiang,Guosheng Ren,Weijun Su
摘要
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.
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