中性粒细胞驱动血管封闭,瘤死亡和转移
Jose M Adrover1,2,3, Xiao Han4,5,6, Lijuan Sun4,5
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. jose.adrover@crick.ac.uk.
Nature
|July 16, 2025
概括
中性粒细胞通过形成阻塞血管的中性粒细胞外陷 (NETs) 来积极导致瘤亡. 阻断NET可以减少瘤缩和转移,从而揭示出新的治疗点.
科学领域:
- 癌症学
- 免疫学
- 细胞生物学
背景情况:
- 瘤亡与癌症预后不佳有关,此前被认为是营养缺乏的被动后果.
- 导致瘤死亡的确切机制及其与转移的关联尚不完全理解.
研究的目的:
- 研究中性粒细胞在诱导瘤死亡中的作用.
- 阐明中性粒细胞导致瘤血管封闭和亡的机制.
- 探索向中性粒细胞活动以抑制瘤进展和转移的潜力.
主要方法:
- 利用多种癌症小鼠模型研究中性粒细胞种群及其功能.
- 标志着特定的瘤引起的中性粒细胞子集 (Ly6G 高 Ly6C 低) 和它们形成中性粒细胞外陷 (NET) 的能力.
- 研究中性粒细胞外陷 (NETs) 对瘤血管,缩和转移的影响,采用遗传和药物抑制策略.
主要成果:
- 鉴定出一种独特的瘤引起的中性粒细胞群,能有效地形成中性粒细胞外陷 (NETs),并有助于血管封闭.
- 观察到这些中性粒细胞聚合物和NETs会引起血管内闭塞,导致瘤缺氧和形亡.
- 证明阻断NET形成可显著减少瘤缩和肺转移,并且周周细胞的癌细胞经历上皮细胞转化为介质细胞.
结论:
- 中性粒细胞通过形成中性粒细胞外陷 (NETs) 积极诱导瘤死亡,导致血管封闭和缺氧.
- 由NET驱动的瘤亡促进了癌细胞上皮细胞转移到介质细胞以及随后的转移.
- 向中性粒细胞外陷 (NET) 形成是一种有前途的治疗策略,可减少瘤亡和癌症转移.
相关概念视频
Metastasis
5.7K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.7K
Inflammation
55.3K
Overview
55.3K
Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
The Tumor Microenvironment
6.8K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K
Cancer Cell Migration through Invadopodia
2.4K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K


