由细胞衍生矩阵诱导的蛋白变化及其对瘤细胞迁移和细胞骨重塑的影响
Adrian A Shimpi1, Erik D Williams2, Lu Ling1
1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States.
ACS biomaterials science & engineering
|November 28, 2023
概括
纤维细胞外基质 (ECM) 加快了瘤细胞的入侵. 使用细胞衍生矩阵 (CDM) 模型和蛋白组学,研究人员发现SRC家族激酶LYN调节了瘤细胞在纤维化ECM上的迁移.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 瘤入侵,转移的最初阶段,是由纤维细胞外基质 (ECM) 沉积驱动的.
- 目前的2D培养中的瘤细胞迁移模型缺乏本地ECM的复杂性,可能会掩盖潜在的机制.
- 专注于精选的途径可能会忽视瘤细胞迁移所涉及的关键信号变化.
研究的目的:
- 用细胞衍生矩阵 (CDM) 模型研究纤维化ECM上的瘤细胞迁移.
- 通过光蛋白组学识别瘤细胞迁移期间由纤维化ECM调节的信号通路.
- 将复杂CDM上的瘤细胞行为与标准组织培养塑料 (TCP) 进行比较.
主要方法:
- 利用细胞衍生矩阵 (CDM) 模型来模仿本地纤维化ECM.
- 采用酸铁的蛋白质组分析来分析信号变化.
- 进行了时间依赖的蛋白质组分析,以确定动态信号事件.
- 通过药理抑制研究了SRC家族激酶LYN的作用.
主要成果:
- 与TCP相比,瘤细胞在CDM上表现出更快,更有方向的迁移.
- 对CDM的迁移变化与细胞扩散的减少和细胞延长的增加有关.
- 酸化焦粘附激酶 (pFAK) +粘附复合物在CDM和TCP之间没有区别.
- 鉴定出SRC家族激酶LYN在两个基质上具有潜在的差异调节和抑制减少迁移.
结论:
- 像CDM这样的体外复杂的物理化学系统对于研究瘤细胞迁移至关重要.
- 蛋白组学与先进模型相结合,可以发现新的信号传递机制.
- SRC家族激酶LYN在调节纤维化ECM上的瘤细胞迁移方面发挥作用,可能与其他途径结合.
相关概念视频
01:35Cancer 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
01:09Cell Migration
17.0K
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
17.0K
02:17The Tumor Microenvironment
6.6K
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...
6.6K
01:32Cytoskeletal Coordination in Cell Migration
4.8K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.8K
01:24Overview of Cell-Matrix Interactions
7.2K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.2K
01:29The Extracellular Matrix
9.0K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
9.0K