Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.
Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.
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DOI：
10.1016/j.mehy.2016.07.009
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发表时间：
2016-09
影响因子：
4.7
通讯作者：
Hood JL
中科院分区：
文献类型：
--
作者：
Hood JL
血管生成是黑色素瘤转移淋巴结准备的关键过程。粒细胞巨噬细胞集落刺激因子（GM-CSF）诱导M1极化巨噬细胞中的缺氧诱导因子1 α（HIF-1α）或M2极化巨噬细胞中的HIF-2α。HIF-1α促进新生血管生成，而HIF-2α促进新生血管的形态正常化。黑色素瘤外泌体在体外诱导内皮细胞表达GM-CSF，在体内诱导转移前淋巴结中表达HIF-1α。这表明黑色素瘤外泌体诱导的内皮GM-CSF和淋巴结中巨噬细胞介导的血管生成之间的关系。理论上，由黑素瘤外来体诱导内皮细胞衍生的GM-CSF在转移前淋巴结中介导不同的血管生成功能，这取决于被膜下窦（SCS）巨噬细胞极性。为了探索这一假设，概述了在淋巴结模型中利用黑色素瘤外泌体的实验。尽管它们具有相反的免疫功能，但通过淋巴结中内皮衍生的GM-CSF间接刺激M1或M2 SCS巨噬细胞的黑色素瘤外泌体可能诱导不同但互补的促肿瘤血管生成过程。
Angiogenesis is a key process in the preparation of lymph nodes for melanoma metastasis. Granulocyte macrophage colony stimulating factor (GM-CSF) induces hypoxia inducible factor 1 alpha (HIF-1α) in M1 or HIF-2α in M2 polarized macrophages. HIF-1α promotes neoangiogenesis while HIF-2α facilitates morphogenic normalization of neovasculature. Melanoma exosomes induce GM-CSF expression by endothelial cells in vitro and HIF-1α expression in pre-metastatic lymph nodes in vivo. This suggest a relationship between melanoma exosome induced endothelial GM-CSF and macrophage mediated angiogenesis in lymph nodes. Theoretically, induction of endothelial cell derived GM-CSF by melanoma exosomes mediates different angiogenic functions in pre-metastatic lymph nodes depending on subcapsular sinus (SCS) macrophage polarity. To explore this hypothesis, experiments utilizing melanoma exosomes in a lymph node model are outlined. Despite their opposing immune functions, indirect melanoma exosome stimulation of M1 or M2 SCS macrophages via endothelial derived GM-CSF in lymph nodes may induce different although complementary pro-tumor angiogenic processes.