The Effects of WW2/WW3 Domains of Smurf2 Molecule on CD4(+)CD25(+)/CD4(+) Proportion in Spleen of 4T1 Tumor Bearing BALB/c Mice

BACKGROUND: TGF-β has long been considered as the main inducer of Tregs in tumor microenvironment and is the reason for the aberrant number of Tregs in tumor-bearing individuals. Recently, it has been suggested that the enzyme arginase I is able to mediate the induction of Tregs in a TGF-β-independent fashion. The recombinant WW2/WW3 domains from Smurf2 molecule was demonstrated to increase TGF-β signaling while reducing arginase I gene expression. In this study, we aimed to examine the effects of this recombinant protein on CD4(+)CD25(+)/CD4(+) proportion in the spleen of 4T1 mammary carcinoma-bearing BALB/c mice. METHODS: Flow cytometry was used to evaluate CD4(+)CD25(+) spleen cell populations of the tumor-bearing mice that received WW2/WW3 protein treatment and those of the control group. RESULTS: The results indicated a significant rise in CD4(+)CD25(+)/CD4(+) ratio, along with an average increase in tumor mass of the subjects that underwent protein treatment. CONCLUSION: It can be inferred that the heightened CD4(+)CD25(+)/CD4(+) proportion in the spleen of protein-treated tumor-bearing mice can be the result of the increased TGF-β signaling despite the reduced arginase I expression.