Search

Purpose. CD147, also known as BSG, is a type I transmembrane glycoprotein that belonged to immunoglobulin superfamily. Mature CD147 is an N-linked glycosylated protein and exists on the transmembrane and as soluble forms in tumors. However, the function of CD147 in cell proliferation of bladder cancer (BC) remains to be elucidated. Methods. The study included 159 patients with BC and 68 healthy controls. The expression of CD147 and gasdermin D (GSDMD) was analyzed by immunohistochemistry (IHC). Western blotting was performed to detect the expression of proteins in BC cells. The relationship between CD147 and GSDMD was analyzed by the IHC score. Results. The expression of CD147 was significantly increased in BC when compared to healthy controls, and the level of CD147 was correlated with tumor proliferation characterized by Ki-67, which is a cell proliferation antigen. In addition, CD147 treatment of BC cells increased the expression of GSDMD, leading to increased Ki-67 expression, while CD147 blockade with peptide in BC significantly reduced GSDMD expression, resulting in reduced cell proliferation. Furthermore, overexpression of GSDMD markedly overcame the inhibitory effect of CD147 peptide on tumor proliferation. BC patients with overexpression of CD147 showed correlation with GSDMD and demonstrated significantly poorer prognosis and overall survival rate. Conclusion. These findings suggested that high expression of CD147 contributed to tumor proliferation in BC via GSDMD, which might in turn act as an unfavorable prognostic marker. [ABSTRACT FROM AUTHOR]

Previous studies have established the efficacy of irradiated cancer cells overexpressing GM-CSF or IL-21 as a vaccine. Here we examined whether the vaccine efficacy was greater when both factors were overexpressed together. MB49 bladder cancer cells were transfected with expression plasmid pT7TS encoding mouse GM-CSF and human IL-21, and then irradiated with 100 Gy at 4 days later. The cells (1×107 per animal) were injected subcutaneously into C57BL/6 mice at 0, 4, 8, and 12 days after inoculation with MB49 tumor xenografts. Control animals were injected with MB49 cells transfected with pT7TS encoding GM-CSF or IL-21 on its own. Tumor growth was monitored for 45 days and compared among the groups using repeated-measures ANOVA. Vaccination with irradiated MB49 cells did not affect xenograft growth. Vaccination with irradiated cells overexpressing GM-CSF or IL-21 alone significantly inhibited tumor growth and led to significantly more CD4+ CD8+ T cells and fewer CD4+ Foxp3+ T cells in the spleen and xenograft. These effects were even greater following vaccination with irradiated cells overexpressing both GM-CSF and IL-21. Irradiated bladder cancer cells overexpressing both GM-CSF and IL-21 are more effective than cells expressing either factor alone as a vaccine against bladder cancer. [ABSTRACT FROM AUTHOR]