| Objective :To investigate the effect of VEGF-C(Vascular endothelial growth factor-C) and TIDC(Tumor infiltrating dendritic cells) in gastric cancer and whether VEGF-C can inhibit the differentiation and function of DCs(dendritic cells),so as to find the new target for the biotherapy of gastric cancer.Methods: 1.The expression of VEGF-C and TIDC in fifty-two specimens of gastric cancer was examined by immunohistochemical staining(S-ABC method). 2. Every cord blood sample was divided equally into three portions,and they were belonged to three groups: group A(the blank control model group), group B(add rhVEGF-C into the culture on the first day, and make the concentration of rhVEGF-C become 25ng/ml in the culture), group C (add rhVEGF-C into the culture on the first day, and make the concentration of rhVEGF-C become 100ng/ml in the culture). 3. The mononuclear cytes were isolated by density gradient centrifugation from cord blood,and the cytes were cultured with the combination of rhGM-CSF, rhIL-4 and rhTNF-α,then the cells were harvested on the 11th day. 4. The cellular morphological features were observed by inverted phase contrast microscope, the surface molecules (CD80, CD83, CD1a and HLA-DR) of the induced cells were analyzed by flow cytometry (FCM), and the amount of IL-12 in culture supernatant was measured by ELISA.Results: 1. Twenty-nine out of fifty-two specimens of gastric cancer (55.77%)showed positive expression of VEGF-C protein. The expression of VEGF-C wasn't associated with sex and age of gastric cancer patients (P>0.05), but was associated with gastric cell differention, invasion depth, lymph node metastasis and stage of TNM (P<0.05) .The probabilities of serosa invasion , lymph node metastasis and III/IV stage of TNM-classification in gastric cancer with VEGF-C expression were larger than that in gastric cancer without VEGF-C expression(P<0.05). 2. The density of TIDC wasn't associated with sex , age of gastric cancer patients or gastric cell differention(P>0.05), but was associated with invasion depth, lymph node metastasis and stage of TNM(P<0.05).The probabilities of serosa invasion , lymph node metastasis and III/IV stage of TNM-classification in the gastric cancer tissue with high density of TIDC are smaller than that in gastric cancer with low density of TIDC(P<0.05). 3. There is a close negative relation between the expression of VEGF-C and the density of tumor infiltrating dendritic cells in gastric cancer (P<0.05). 4. There is no statistical differences between group A and group B on the expressions of cell surface molecules(CD80, CD83, CD1a and HLA-DR) and the concentration of IL-12 in culture supernatant. Compared with group A, the expression of the DCs surface molecules CD80, CD83, CD1a and HLA-DR in group C was significantly decreased (P<0.05) ,and the amount of IL-12 in culture supernatant of group C was significantly lower than it in group A (P<0.05).Conclusions: 1.Both the expression VEGF-C protein and the density of TIDC are associated with the invasion and metastasis of gastric cancer. VEGF-C can facilitate the invasion and metastasis through promote the emerge of lympgatic vessels, and high density of TIDC probably can inhibit the invasion and metastasis of gastric cancer. 2. VEGF-C protein secreted by tumor cells probably decrease the density of TIDC in gastric cancer, and rhVEGF-C can inhabit the differentiation and function of dendritic cells derived from cord blood in vitro, supporting VEGF-C secreted by gastric cancer cell can inhabit the differentiation and function of DCs in vivo. 3. To sum up, VEGF-C secreted by gastric cancer cells can enhance the invasion and metastasis of gastric cancer by promoting the emerge of lympgatic vessels and probably inhabit the differentiation and function of DCs, supporting that blocking the effort of VEGF-C might be a new way for biotherapy of gastric cancer. |
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