集成蛋白β8通过调节CCL5促进LUAD进展,促进巨细胞透和极化
1Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 13, 2024
概括
集成蛋白β8 (ITGβ8) 通过促进M2巨细胞两极分化,驱动肺腺癌的进展. 这种相互作用涉及CCL5和PI3K/AKT/IRF9信号,创建一个反循环,使患者的预后恶化.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 瘤微环境 (TME) 极大地影响癌症的进展和转移.
- 整合素β8 (ITGβ8),是整合素家族的关键成员,在许多癌症中表达高.
- ITGβ8在肺腺癌 (LUAD) 中的作用及其与巨细胞的相互作用需要进行详细的研究.
研究的目的:
- 研究因特林β8 (ITGβ8) 在调解肺腺癌 (LUAD) 细胞和巨细胞之间的相互作用中的作用.
- 阐明ITGβ8诱导的巨细胞极化背后的分子机制及其对LUAD进展的影响.
- 在ITGβ8-巨信号轴内识别潜在的治疗点.
主要方法:
- 在LUAD患者样本中分析ITGβ8表达水平和与临床结果的相关性.
- 使用LUAD细胞 (A549) 和THP-1衍生的巨细胞进行共同培养实验,以评估ITGβ8对巨细胞两极分化的影响.
- 调查信号通路,包括CCL5,PI3K/AKT/IRF9和SPI1,参与ITGβ8-巨细胞交叉.
- 来自共同培养的条件介质 (TCM) 的分析,以评估对LUAD细胞增殖和侵入的影响.
主要成果:
- 在LUAD中增加ITGβ8表达与较高的CD163+巨细胞透和较差的患者预后相关.
- 在LUAD细胞中ITGβ8的过度表达会在THP-1巨细胞中诱导M2样极化.
- ITGβ8介导的巨细胞极化取决于CCL5和PI3K/AKT/IRF9通路.
- 类似M2的巨细胞分泌IL8和IL10,这些巨细胞反过来通过SPI1通过LUAD细胞上调ITGβ8的表达,建立一个反循环.
结论:
- 集成蛋白β8 (ITGβ8) 是肺腺癌细胞和巨细胞之间交叉的关键媒介.
- 一个积极的反循环存在,ITGβ8促进M2巨分化,随后,M2巨增强ITGβ8在LUAD细胞中的表达.
- 针对ITGβ8-巨轴为LUAD提供了一个潜在的治疗策略.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
Activation of Integrins
3.3K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.3K
Integrins
3.8K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
3.8K
Cancer Cell Migration through Invadopodia
2.3K
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,...
2.3K
Selectins
3.3K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
3.3K


