Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer

(E-pub Ahead of Print)

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

Journal Name: Current Pharmaceutical Design

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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.

Conclusions: Calpains are activated in stromal cells, including pancreatic stellate cells and mesenchymal cells, thereby inducing 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.

Keywords: tumorigenesis, extracellular matrix, vascular endothelial cells, tumor neovessels, fibrosis, desmoplasia, wound

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(E-pub Ahead of Print)
DOI: 10.2174/1381612827666210311143053
Price: $95

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