淋巴管新生
淋巴管内皮
淋巴系统
转移
癌症研究
趋化因子
肿瘤微环境
血管生成
下调和上调
生物
医学
病理
免疫学
癌症
免疫系统
内科学
基因
生物化学
肿瘤细胞
作者
Xiaojing Chen,Wen-Fei Wei,Zi-Ci Wang,Nisha Wang,Chu-Hong Guo,Chenfei Zhou,Luo-Jiao Liang,Sha Wu,Liang Li,Wei Wang
出处
期刊:Angiogenesis
[Springer Nature]
日期:2021-01-23
卷期号:24 (3): 549-565
被引量:28
标识
DOI:10.1007/s10456-020-09766-2
摘要
Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C-C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment.
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