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.
