Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer

Title:Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer

Volume: 27 Issue: 28

Author(s): Takuro Miyazaki*, Risako Akasu and Akira Miyazaki

Affiliation:

• Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555,Japan

Keywords: Tumorigenesis, extracellular matrix, vascular endothelial cells, tumor neovessels, fibrosis, desmoplasia, wound healing.

Abstract:

Background: 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.

Objective: Here, we shed light on the recent advances that have been made in understanding how calpain contributes to stromal regulation in cancer.

Conclusion: 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.

Cite this article as:

Miyazaki Takuro *, Akasu Risako and Miyazaki Akira, Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer, Current Pharmaceutical Design 2021; 27 (28) . https://dx.doi.org/10.2174/1381612827666210311143053