在3D培养中癌细胞沉积揭示了由自我生成的梯度和粘附部位调节的活跃迁移
Nikolaos M Dimitriou1, Salvador Flores-Torres1, Maria Kyriakidou2
1Department of Bioengineering, McGill University, Montreal, QC, Canada.
PLoS computational biology
|June 11, 2024
概括
癌细胞在3D培养中积极向下迁移,这种现象受到粘附和药物治疗的影响. 了解这种细胞沉积提供了对癌症机械生物学和治疗策略的见解.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 细胞机械生物学 细胞机械生物学
背景情况:
- 细胞沉积或3D培养中的向下迁移是鲜为人知的.
- 这种现象可能会影响癌症的发展和治疗疗效.
- 在3D环境中研究细胞迁移对于了解瘤进展至关重要.
研究的目的:
- 在3D癌细胞培养中研究细胞沉积现象.
- 探索粘附,药物治疗 (Paclitaxel) 和与纤维细胞共同培养在细胞迁移中的作用.
- 开发和验证细胞沉积的数学模型.
主要方法:
- 在3D水凝培养中使用三阴性乳腺癌细胞的多尺度实验方法.
- 在不同的条件下检查细胞迁移:帕克利塔塞尔存在/不存在,粘附性高/低,与纤维细胞共同培养.
- 基于通过自我生成的化学变化梯度的活跃迁移的数学模型的开发.
主要成果:
- 观察和建模了细胞沉积,这表明由自我生成的化学反应梯度驱动的活跃迁移.
- 迁移似乎是由MAPK和TGF-β通路调节的.
- 帕克利塔克塞尔治疗显著降低了随机运动和向,提高了模型的准确性.
- 在低附着性和共同培养条件下减少沉积,由于细胞分泌的信号,支持活跃的向下迁移.
结论:
- 在3D培养中细胞沉积是一种积极的,有针对性的迁移过程,而不是被动的沉积.
- 这种迁移受到细胞微环境的影响,包括粘附和细胞-细胞信号传递.
- 数学建模为理解和预测3D培养中的细胞行为提供了定量框架,这对癌症治疗有意义.
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
01:21Chemotaxis and Direction of Cell Migration
3.4K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.4K
01:19Cell Migration
4.8K
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
4.8K