Corro Néstor, Alarcón Sebastián, Astroza Ángel, González-Stegmaier Roxana, Añazco Carolina
Nutritional Biochemistry Laboratory, School of Nutrition and Dietetics, Faculty of Rehabilitation and Quality of Life Sciences, Universidad San Sebastián, Valdivia 5091000, Chile.
Departamento de Ciencias Biológicas y Químicas, Facultad de Ciencias, Universidad San Sebastián, Sede Valdivia, Valdivia 5091000, Chile.
Biology (Basel). 2025 Aug 16;14(8):1067. doi: 10.3390/biology14081067.
The tumor microenvironment (TME) has a substantial impact on the progression of gastric cancer. Collagen, the most abundant protein in the extracellular matrix (ECM), forms a dense physical barrier that regulates anti-tumor immunity in the TME. It is a significant regulator of the signaling pathways of cancer cells, which are responsible for migration, proliferation, and metabolism. ECM proteins, particularly remodeling enzymes and collagens, can be modified to increase stiffness and alter the mechanical properties of the stroma. This, in turn, increases the invasive potential of tumor cells and resistance to immunotherapy. Given the dynamic nature of collagen, novel therapeutic strategies have emerged that target both collagen biosynthesis and degradation, processes that are essential for addressing ECM stiffening. This review delineates the upregulation of the expression and deposition of collagen, as well as the biological functions, assembly, and reorganization that contribute to the dissemination of this aggressive malignancy. Furthermore, the review emphasizes the importance of creating 3D in vitro models that incorporate innovative biomaterials that avoid the difficulties of traditional 2D culture in accurately simulating real-world conditions that effectively replicate the distinctive collagen microenvironment. Ultimately, it investigates the use of decellularized ECM-derived biomaterials as tumor models that are designed to precisely replicate the mechanisms associated with the progression of stomach cancer.
肿瘤微环境（TME）对胃癌的进展有重大影响。胶原蛋白是细胞外基质（ECM）中最丰富的蛋白质，形成了一个致密的物理屏障，调节TME中的抗肿瘤免疫。它是癌细胞信号通路的重要调节因子，这些信号通路负责细胞迁移、增殖和代谢。ECM蛋白，特别是重塑酶和胶原蛋白，可以被修饰以增加硬度并改变基质的力学性能。反过来，这增加了肿瘤细胞的侵袭潜力和对免疫疗法的抗性。鉴于胶原蛋白的动态性质，已经出现了针对胶原蛋白生物合成和降解的新型治疗策略，这些过程对于解决ECM硬化至关重要。本综述阐述了胶原蛋白表达和沉积的上调，以及有助于这种侵袭性恶性肿瘤扩散的生物学功能、组装和重组。此外，该综述强调了创建三维体外模型的重要性，这些模型结合了创新的生物材料，避免了传统二维培养在准确模拟有效复制独特胶原蛋白微环境的真实条件方面的困难。最终，它研究了使用脱细胞ECM衍生的生物材料作为肿瘤模型，旨在精确复制与胃癌进展相关的机制。
