Activating transcription factor 4 promotes angiogenesis of breast cancer through enhanced macrophage recruitment.
Activating transcription factor 4 promotes angiogenesis of breast cancer through enhanced macrophage recruitment.
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激活转录因子 4 通过增强巨噬细胞募集促进乳腺癌血管生成。
DOI：
10.1155/2015/974615
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发表时间：
2015
影响因子：
--
通讯作者：
Su W
中科院分区：
文献类型：
--
作者：
Liu C;Li Z;Wang L;Tong L;He N;Chen Y;Liu Y;Wu Z;Sun P;Xiang R;Ren G;Su W
血管生成在肿瘤的发生、发展过程中起重要作用。肿瘤血管生成除了受肿瘤细胞本身的调控外，还受到肿瘤微环境中的基质细胞如肿瘤相关巨噬细胞的影响。转录激活因子4（ATF 4）是ATF/CREB家族的成员，已被报道与肿瘤血管生成有关。在这项研究中，我们发现在小鼠乳腺癌细胞中外源性过表达ATF 4通过增加肿瘤微血管密度促进肿瘤生长。然而，在该模型中，ATF 4过表达未能增加肿瘤细胞中包括血管内皮生长因子A（VEGFA）在内的一系列促血管生成因子的表达水平。因此，我们进一步研究了促血管生成巨噬细胞在肿瘤组织中的浸润，发现过表达ATF 4的肿瘤可以通过分泌巨噬细胞集落刺激因子（M-CSF）募集更多的巨噬细胞。总之，我们得出结论，乳腺癌细胞中外源性过表达ATF 4可能有助于巨噬细胞向肿瘤组织中的募集，并间接促进肿瘤血管生成和肿瘤生长。
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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影响因子：
3.5
作者：
Takanami, I;Takeuchi, K;Kodaira, S
通讯作者：
Kodaira, S
影响因子：
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作者：
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11.2
作者：
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影响因子：
50.3
作者：
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通讯作者：
De Palma, Michele
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影响因子：
11.2
作者：
Chen, Wei;Ma, Tao;Liang, Ting-bo
通讯作者：
Liang, Ting-bo