Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, P. R. China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, P. R. China.
Small. 2024 Sep;20(36):e2309907. doi: 10.1002/smll.202309907. Epub 2024 May 7.
The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell-ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin-collagen interplay reinforces the central role of integrins in mediating cell-ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell-ECM interactions, which may facilitate the development of novel therapeutic horizons.
细胞外基质（ECM）的生物物理特性通过细胞-ECM 相互作用在调节癌症进展方面起着关键作用。然而，胃癌（GC）的生物物理特性在很大程度上仍未得到探索。值得注意的是，GC ECM 表现出明显的异质变形，例如基质变硬和复杂的重构。本研究通过将 I 型胶原和藻酸盐结合，设计了一种体外仿生水凝胶平台，可在生理硬度范围内独立调节基质的硬度和结构，同时保持一致的胶原浓度和纤维形貌。利用该平台，本研究评估了基质生物物理特性对 AGS 细胞增殖、迁移、侵袭和其他关键动力学的影响。研究结果突出了基质硬度和结构之间的强烈相互作用，影响细胞反应和 ECM 重塑。此外，对整合素/肌动蛋白-胶原相互作用的研究强调了整合素在介导细胞-ECM 相互作用中的核心作用，反过来又塑造了细胞行为和 ECM 适应。总之，本研究揭示了 ECM 生物物理特性在 GC 恶性潜能中的一个以前未被识别的作用，并深入了解了双向机械细胞-ECM 相互作用，这可能有助于开辟新的治疗途径。
