Leptin/LPS-treated dendritic cells reduce the expression of genes involved in tumor tissue metastasis and angiogenesis in an animal model of breast cancer.

Abstract

Leptin, an immune-regulating protein, enhances the maturation of dendritic cells (DCs). We previously demonstrated that leptin and lipopolysaccharide (LPS) promote the expression of co-stimulatory molecules on the surface of DCs. Leptin/LPS-treated DCs increased T cell responses against 4T1 breast cancer in mice. Therefore, in the present study, we investigate the effects of a DC vaccine treated with leptin and LPS on the genes involved in tumor metastasis, angiogenesis, and related cytokines in a mouse model of breast cancer. Tumor induction was achieved through subcutaneous injection of 4T1 cells into syngeneic mice. On days 12 and 19, the mouse groups received the DC vaccine treated with leptin and a combination of leptin and LPS. After sacrificing the mice on day 26, the levels of IL-6 and IL-33 in the serum were assayed using the ELISA technique, and the expression levels of the VEGF, CCL2, MMP9, and CCL5 genes in the tumors were measured by Real-Time PCR. Compared to untreated tumor-bearing mice, the leptin-treated mature DC (mDC) group exhibited a significant reduction in the expression of MMP9 (0.33-fold, p = 0.01) and CCL5 (0.81-fold, p = 0.02). The leptin-LPS-treated mDC group showed decreased expression of genes involved in metastasis and tumor growth, including VEGF (0.72-fold, p = 0.03), MMP9 (0.26-fold, p = 0.001), and CCL5 (0.3-fold, p = 0.006), indicating more efficient prevention of metastasis. The CCL2 gene expression levels in both treatment groups showed a slight decreasing trend, but these changes were not statistically significant. The leptin-treated mDC group reduced IL-6 production by approximately 16% (p = 0.02), while treatment with the leptin-LPS-treated mDC significantly decreased IL-6 production by approximately 22% (p = 0.01) and increased IL-33 production by approximately 42% (p = 0.03). The findings of the present study indicate that the leptin-LPS-treated mDC vaccine group reduced the expression of genes and cytokines involved in metastasis and angiogenesis, demonstrating greater efficacy compared to the leptin-treated mDC vaccine group.