ABSTRACT: Vascular endothelial growth factor (VEGF) is a tumor angiogenesis factor that is important in immune regulation. In our previous study, we found that VEGF expression in the peripheral blood and neoplasm nest from patients with oral squamous cell carcinoma (OSCC) was positively correlated with the course of disease, while an inverse correlation between VEGF expression and dendritic cells (DCs) was identified in the peripheral blood. Therefore, in the present study, we investigated whether inhibition of human VEGF in the human tongue carcinoma cell line Tca8113 had effects on the activity of monocyte-derived DCs. We knocked down the expression of human VEGF in Tca8113 cells using the small interfering RNA (siRNA) technique. Tca8113 cells pre-transfected with siRNA targeting VEGF were co-cultured with monocyte‑derived immature and mature DCs. Cell proliferation was evaluated by a WST-8 assay. Cell apoptosis, cell cycle and cell phenotypes were determined by flow cytometry. The data revealed that downregulation of the human VEGF significantly inhibited the proliferation of Tca8113 cells and increased apoptosis. Inhibition of human VEGF arrested the cell cycle of Tca8113 cells at the G0/G1 phase. Our results showed that the co-culture of DCs with Tca8113 cells markedly inhibited the expression of the mature markers of DCs including HLA-DR, CD80, CD86, CD40 and CD1a, as well as the immature marker CD83, while inhibition of human VEGF in Tca8113 cells significantly reversed these effects. Therefore, human VEGF in Tca8113 cells may not only regulate the cell proliferation and apoptosis of oral squamous cell carcinoma cells, but may also inhibit DC maturation.
Oncology letters 04/2012; 3(4):885-892. · 0.11 Impact Factor
ABSTRACT: To investigate the effect of vascular endothelial growth factor (VEGF) on the differentiation, formation and function of the dendritic cell (DC) in peripheral blood of patients with oral squamous cell carcinoma (OSCC).
Flow cytometry was used to detect the number of DC in peripheral blood of 81 patients with OSCC, and ELISA applied to test serum VEGF concentration the OSCC patients, and immunohistochemistry used to observe the expression of VEGF in primary foci of 57 patients with OSCC. DC from CD-14 peripheral blood mononuclear cells were cultured with VEGF(165) in vitro to investigate the cytokine's effect on DC.
In comparison with controls [(325.70 +/- 117.54) ng/L], the level of serum VEGF [(764.33 +/- 263.64) ng/L] was significantly increased (P < 0.01) and the DC numbers was significantly decreased (P < 0.01) in patients with OSCC. There was a negative correlation between serum VEGF concentration and the level of DC (P < 0.01). The expression of VEGF in primary focus was positively correlated with serum VEGF concentration, but was negatively correlated with the level of peripheral blood DC (P < 0.01). DC cultured in vitro with VEGF(165) decreased the expression of CD-1a, CD-40, CD-80, CD-86, CD-83, HLA-DR, and revealed a lower ability of stimulating T lymphocyte proliferation but a higher ability of uptake, compared to controls.
The overexpressed VEGF in patients with OSCC might be one of the important reasons for blocking the differentiation and maturation of DC.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 04/2009; 44(3):135-9.
ABSTRACT: To investigate the inhibitory effect of dendritic cells (DCs) on the growth of the implanted tongue squamous cell carcinoma (SCC) tumors in nude mice.
Being induced from human peripheral blood monocytes (PBMCs) with rhGM-CSF, rhIL-4 and rhTNF-alpha, DCs were pulsed by Tca8113 cells lysates. Those DCs and T lymphocytes were co-cultured to induce specific cytotoxic T lymphocytes (CTLs). Immunotherapy was then performed after those DCs and CTLs were implanted into the tumor-bearing nude mice.
DCs were induced from PBMCs with multiple cytokines. Compared with the control groups, the growth of tumors was significantly inhibited in the group that had been implanted with DCs and CTLs, and tumor doubling time also increased markedly (P < 0.05).
DCs function normally after being induced from human PBMCs with multiple cytokines; DCs pulsed with tumor cell lysates and CTLs co-cultured with those DCs have a significant anti-tumor immune activity in nude mice.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 03/2006; 41(2):81-4.