Cystatin C regulates cell division in primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is associated with cerebral inflammation characterized by elevated neutrophils, monocytes, platelets, and lymphocytes. However, the comprehensive profile of inflammation-related molecules in PCNSL remains unclear. In this study, we conducted proteomic analysis of PCNSL tissue compared with normal brain to identify factors influencing neuroinflammation and potential therapeutic targets. In contrast to the general elevation of inflammatory molecules, cystatin C (Cyst C) showed markedly reduced expression. This result was confirmed by western blotting and mRNA analysis. Immunohistochemistry revealed widespread Cyst C positivity in glial cells of the normal brain, whereas PCNSL tissue was dominated by Cyst C-negative B cells. To further investigate its role, cultured PCNSL cells were treated with recombinant human Cyst C. Treatment reduced viable cell counts in a dose- and time-dependent manner over 4 days without inducing cell death, indicating inhibition of cell division. Immunohistochemistry demonstrated that Cyst C increased p21 expression and decreased cyclin-dependent kinase 1 and Cyclin B. These findings identify Cyst C as a regulator of PCNSL cell division, highlighting it as a potential therapeutic target.