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3D collagen architecture regulates cell adhesion through degradability, thereby controlling metabolic and oxidative stress.
Integrative Biology ( IF 2.5 ) Pub Date : 2019-05-01 , DOI: 10.1093/intbio/zyz019
Daniel O Velez 1 , Sural K Ranamukhaarachchi 1 , Aditya Kumar 1 , Rishi N Modi 1 , Esther W Lim 1 , Adam J Engler 1 , Christian M Metallo 1 , Stephanie I Fraley 1, 2
Affiliation  

The collagen-rich tumor microenvironment plays a critical role in directing the migration behavior of cancer cells. 3D collagen architectures with small pores have been shown to confine cells and induce aggressive collective migration, irrespective of matrix stiffness and density. However, it remains unclear how cells sense collagen architecture and transduce this information to initiate collective migration. Here, we tune collagen architecture and analyze its effect on four core cell-ECM interactions: cytoskeletal polymerization, adhesion, contractility, and matrix degradation. From this comprehensive analysis, we deduce that matrix architecture initially modulates cancer cell adhesion strength, and that this results from architecture-induced changes to matrix degradability. That is, architectures with smaller pores are less degradable, and degradability is required for cancer cell adhesion to 3D fibrilar collagen. The biochemical consequences of this 3D low-attachment state are similar to those induced by suspension culture, including metabolic and oxidative stress. One distinction from suspension culture is the induction of collagen catabolism that occurs in 3D low-attachment conditions. Cells also upregulate Snail1 and Notch signaling in response to 3D low-attachment, which suggests a mechanism for the emergence of collective behaviors.

中文翻译:

3D 胶原蛋白结构通过可降解性调节细胞粘附,从而控制代谢和氧化应激。

富含胶原蛋白的肿瘤微环境在指导癌细胞的迁移行为中起着至关重要的作用。具有小孔的 3D 胶原蛋白结构已被证明可以限制细胞并诱导积极的集体迁移,而与基质刚度和密度无关。然而,目前尚不清楚细胞如何感知胶原蛋白结构并转导这些信息以启动集体迁移。在这里,我们调整胶原结构并分析其对四种核心细胞-ECM 相互作用的影响:细胞骨架聚合、粘附、收缩性和基质降解。从这一综合分析中,我们推断出基质结构最初会调节癌细胞的粘附强度,这是由结构引起的基质降解性变化的结果。也就是说,孔隙较小的结构不易降解,癌细胞粘附到 3D 纤维胶原蛋白需要可降解性。这种 3D 低附着状态的生化后果与悬浮培养诱导的生化后果相似,包括代谢和氧化应激。与悬浮培养的一个区别是在 3D 低附着条件下诱导胶原分解代谢。细胞还上调 Snail1 和 Notch 信号以响应 3D 低附着,这表明了集体行为出现的机制。与悬浮培养的一个区别是在 3D 低附着条件下诱导胶原分解代谢。细胞还上调 Snail1 和 Notch 信号以响应 3D 低附着,这表明了集体行为出现的机制。与悬浮培养的一个区别是在 3D 低附着条件下诱导胶原分解代谢。细胞还上调 Snail1 和 Notch 信号以响应 3D 低附着,这表明了集体行为出现的机制。
更新日期:2019-06-28
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