多效蛋白
血管生成
炎症性乳腺癌
转移
乳腺癌
癌症
医学
癌症研究
祖细胞
新生血管
细胞因子
病理
免疫学
内科学
生物
干细胞
细胞生物学
生长因子
受体
作者
M. Zhang,Kaiwen Zhou,Z J Wang,Ting Liu,Laura E. Stevens,Filipa Lynce,Wendy Y. Chen,Sui Peng,Yubin Xie,Duanyang Zhai,Qianjun Chen,Yi Shi,Huijuan Shi,Zhongyu Yuan,Xiaoping Li,Juan Xu,Zhenhai Cai,Jianping Guo,Nan Shao,Ying Lin
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-03-20
标识
DOI:10.1158/0008-5472.can-23-2640
摘要
Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in IBC patients, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for crosstalk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.
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