Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Curr Pharm Des. 2021;27(28):3128-3138. doi: 10.2174/1381612827666210311143053.
Normalization of the stromal microenvironment is a promising strategy for cancer control. Cancer-associated fibroblasts, tumor-associated macrophages, and mesenchymal stromal cells have a central role in stromal functions. Accordingly, understanding these stromal cells is indispensable for the development of next-generation cancer therapies. Growing evidence suggests that calpain-induced intracellular proteolysis is responsible for cancer growth and stromal regulation. Calpain is a family of stress-responsive intracellular proteases and is inducible in cancer and stromal cells during carcinogenesis.
Here, we shed light on the recent advances that have been made in understanding how calpain contributes to stromal regulation in cancer.
Calpains are activated in stromal cells, including pancreatic stellate cells and mesenchymal cells. They induce fibrogenic responses in cancer stroma. Moreover, these molecules contribute to epithelial-mesenchymal transition and endothelial-mesenchymal transition to provide mesenchymal stromal cells in the microenvironment and concomitantly participate in cancer angiogenesis. In addition to the conventional calpains, the unconventional calpain-9 is associated with epithelial-mesenchymal transition. Animal experiments showed that targeting calpain systems antagonizes cancer development; thus, this approach is promising for cancer control.
基质微环境的正常化是癌症控制的一种很有前途的策略。癌症相关成纤维细胞、肿瘤相关巨噬细胞和间充质基质细胞在基质功能中起着核心作用。因此，了解这些基质细胞对于开发下一代癌症疗法是必不可少的。越来越多的证据表明，钙蛋白酶诱导的细胞内蛋白水解负责癌症的生长和基质的调节。钙蛋白酶是一类应激反应性细胞内蛋白酶，在癌症发生过程中可在癌症和基质细胞中诱导。
本文旨在阐明钙蛋白酶在癌症基质调节中的作用的最新研究进展。
钙蛋白酶在基质细胞（包括胰腺星状细胞和间充质细胞）中被激活。它们在肿瘤基质中诱导纤维生成反应。此外，这些分子有助于上皮-间充质转化和内皮-间充质转化，为微环境中的间充质基质细胞提供，并同时参与癌症血管生成。除了传统的钙蛋白酶外，非传统的钙蛋白酶-9与上皮-间充质转化有关。动物实验表明，靶向钙蛋白酶系统可拮抗癌症的发展；因此，这种方法有望用于癌症控制。
