The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China; Key laboratory of biotherapy and regenerative medicine, The first hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000, China.
The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China; Key laboratory of biotherapy and regenerative medicine, The first hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000, China; Department of general surgery, The first hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000, China.
Acta Biomater. 2022 Sep 15;150:34-47. doi: 10.1016/j.actbio.2022.08.005. Epub 2022 Aug 7.
The tumor microenvironment (TME) is a complex macromolecular network filled with a series of stromal cells. It plays an important role in tumorigenesis, development, immune escape, drug resistance, and other processes and has received increasing attention in recent years. Currently, tumor cell-centered treatments are insufficient to eradicate malignancies, and researchers are constantly searching for better treatments. Over the past decade, the TME has been recognized as a rich resource for anti-cancer drug development. As a significant mechanical feature in the microenvironment of solid tumors, matrix stiffness is increased owing to stromal deposition and remodeling. The effect of matrix stiffness on cancer cells has been described in many studies, whereas its effect on cancer stromal cell fate has rarely been summarized. Therefore, this review discusses the relevant content and drug treatment studies targeting matrix stiffness. STATEMENT OF SIGNIFICANCE: Biochemical and biophysical interactions between tumor cells, stromal cells, and the extracellular matrix (ECM) co-create a distinct tumor microenvironment (TME), which impacts disease outcome. In recent years, there has been a greater emphasis on the physical properties of the ECM, with matrix stiffness being one of the most thoroughly investigated. The matrix stiffness of solid tumors is now commonly acknowledged to be greater than that of normal tissues. Cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and endothelial cells (ECs) can all respond to matrix stiffness. At the same time, our current understanding of the TME is insufficient, and an in-depth examination of interactions between ECM and cells could lead to the development of more efficient and specialized treatments.
肿瘤微环境（TME）是一个充满一系列基质细胞的复杂大分子网络。它在肿瘤发生、发展、免疫逃逸、耐药等过程中起着重要作用，近年来受到越来越多的关注。目前，以肿瘤细胞为中心的治疗方法不足以根除恶性肿瘤，研究人员一直在不断寻找更好的治疗方法。在过去的十年中，TME 已被认为是开发抗癌药物的丰富资源。作为实体瘤微环境中的一个重要力学特征，基质硬度因基质沉积和重塑而增加。许多研究描述了基质硬度对癌细胞的影响，但很少有研究总结其对肿瘤基质细胞命运的影响。因此，本文讨论了靶向基质硬度的相关内容和药物治疗研究。
肿瘤细胞、基质细胞和细胞外基质（ECM）之间的生化和生物物理相互作用共同创造了独特的肿瘤微环境（TME），影响着疾病的结局。近年来，人们更加关注 ECM 的物理性质，其中基质硬度是研究最透彻的性质之一。固体肿瘤的基质硬度现在通常被认为大于正常组织。成纤维细胞、肿瘤相关巨噬细胞（TAMs）和内皮细胞（ECs）都可以对基质硬度做出反应。同时，我们对 TME 的理解还不够深入，深入研究 ECM 和细胞之间的相互作用可能会导致开发出更有效和更有针对性的治疗方法。
