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Pancreatic cancer is one of the most lethal types of cancer, and curative resection is only applicable to potentially limited cases due to early metastasis and local invasion. This study reports the influence of CXCL12 and its receptor CXCR4 on the progression of pancreatic cancer and highlights the correlation between the CXCL12/CXCR4 axis and the organ-specific metastasis of pancreatic adenocarcinoma (PAC). A total of 34 patients with pancreatic cancer participated in the current study. The expression of CXCL12 and CXCR4 in cancerous tissues, paracancerous tissues, normal pancreas and lymph nodes surrounding the pancreas were investigated using immunohistochemistry and RT-PCR; furthermore, their relationship with clinicopathological factors was explored (PV9000 method). The positive rate of CXCL12 protein was 13.3% (4/30), the positive rate of CXCR4 protein was 80% (24/30) in tumor tissues. Additionally, a significant correlation between the expression pattern of the CXCL12/CXCR4 axis with lymph node metastasis was identified (P0.05). Also, the positive rate of CXCL12 protein was 50% (15/30), the positive rate of CXCR4 protein was 73.3% (22/30) in the lymphocytes in lymph nodes surrounding the pancreas. Furthermore, we found that CXCL12 and CXCR4 expression in paratumorous vessels and neural tissue were significantly strongly positive. The paratumorous vessels and neural tissue with positive CXCL12 and CXCR4 expression were invaded by CXCL12-positive pancreatic cancer cells. The chemotactic interaction between CXCR4 and its ligand CXCL12 may be a critical event during the progression of pancreatic cancer. The CXCL12/CXCR4 axis plays an important role in the progression and organ-specific metastasis of pancreatic adenocarcinoma.

In this study, we report the influence of CCL21 and its receptor, CCR7, on the progression of pancreatic cancer and illuminates the correlation between the CCL21/CCR7 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). A total of 30 patients with pancreatic cancer was involved in the current study. The expression of CCL21 and CCR7 in cancerous tissues, paracancerous tissues and normal pancreas were investigated using real-time PCR, Western blot and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. Compared to paracancerous tissues and normal pancreas, CCL21 expression in cancerous tissues was detected at a significantly low level. In contrast, the CCR7 expression was considerably higher in cancerous tissues than in normal pancreas and paracancerous tissues. Additionally, a significant correlation between the expression pattern of the CCL21/CCR7 axis and clinicopathological features, such as lymph node metastasis, was identified. Furthermore, we found that CCL21 expression was significantly associated with MVD but not significantly associated with MLVD, while CCR7 expression was significantly associated with MLVD but not significantly associated with MVD. The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemotactic interaction.

Background : We analyzed the intratumoral and peritumoral microvessel density (MVD) and microlymphatic vessel density (MLVD) in pancreatic adenocarcinoma (PAC) and recorded the expression of vascular endothelial growth factor (VEGF)-C and -D. These data were tested for their significance for tumor progression. Methods : The tissue samples were obtained from 30 patients with PAC. The expression of VEGF-C and -D, MLVD, MVD was assayed by immunohistochemical staining. The expression of VEGF-A and -C, and -D mRNA was detected by semi-quantitative RT-PCR. Results : Immunohistochemical analysis revealed the presence of VEGF-C and -D immunoreactivity in 73% (22/30) and 57% (17/30). The positive rates of VEGF-C and -D protein in central portion of tumors (30% and 16.7%) were significantly lower than those in marginal portion (73.3% and 56.7%). The group with high expression of VEGF-C and -D in marginal portion had higher incidence of lymph node metastasis, lymphatic invasion and venous invasion. The MLVD in both of the VEGF-C and -D positive groups was higher than that in the negative groups, and the lymph node metastasis increased. MVD in the VEGF-C positive group was higher than that in the negative group. Conclusions : The expression of VEGF-C and -D in the marginal portion of tumor significantly associated with lymphatic metastasis and prognosis in patients with PAC, and may induced lymphangiogenesis. VEGF-C was important in the regulation of angiogenesis and lymphangiogenesis in PAC.

The aim of this study was to investigate induction of apoptosis by the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and gemcitabine in the pancreatic cancer cell line SW1990. The sensitivity of SW1990 cells to TRAIL and/or gemcitabine-induced apoptosis and the rate of apoptosis were assessed by MTT assay and flow cytometry, respectively. We used Hoechst 33342 staining to observe apoptotic morphology and expression levels of proteins were analyzed by Western blottin. Growth inhibition and apoptosis rates on treatment with the combination of TRAIL and gemcitabine were significantly higher than with each drug alone (p0.05). Pancreatic cancer cells exhibited a typical apoptosis morphology after treatment with TRAIL or gemcitabine. The levels of cellular apoptosis-associated proteins such as Smac/DIABLO, Cyto C, and the activated fragment of caspase-3 (P17) increased, but the expression of XIAP was significantly decreased after 24 h (p0.05). SW1990 cells responded to TRAIL and/or gemcitabine-induction of apoptosis in a time and concentration-dependent manner. The mechanism of the apoptosis-sensitization effect appeared associated with significant up-regulation of Smac/DIABLO and cytochrome C, down-regulation of XIAP, and activation of caspase-3.

Background This study reports the influence of CXCL12 and its receptor CXCR4 on the progression of pancreatic cancer and illuminates the correlation between the CXCL12/CXCR4 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). Methods A total of 30 patients with pancreatic cancer participated in the current study. The expression of CXCL12 and CXCR4 in cancerous tissues, paracancerous tissues, normal pancreas, and lymph nodes surrounding the pancreas were investigated using real-time PCR and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. Results CXCL12 expression in tumor tissues was significantly lower than that of paracancerous tissues, normal pancreas, and lymph nodes. In contrast, CXCR4 expression in cancerous tissues was considerably higher than that of normal pancreas. Additionally, a significant correlation between the expression pattern of the CXCL12/CXCR4 axis and clinicopathologic features, such as lymph node metastasis, was identified. Furthermore, we found that CXCL12 expression was significantly associated with MVD but not significantly associated with MLVD, while CXCR4 expression was significantly associated with MLVD but not significantly associated with MVD. Conclusions The chemotactic interaction between CXCR4 and its ligand CXCL12 may be a critical event during the progression of pancreatic cancer. The underlying mechanism may be the induction of angiogenesis and lymphangiogenesis regulated by the interaction of CXCL12 and CXCR4.

To investigate the expression of CXCL12, its receptor CXCR4 and its correlations with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC).The tissue samples were obtained from 30 patients with PAC by surgery between January 2005 and December 2007, which including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes. The patients age ranged from 35 to 78 years old (median 57.2 years old). The expressions of CXCL12 and CXCR4 in these tissues were assayed by immunohistochemical staining, RT-PCR and fluorescence quantitative real-time PCR.In the immunohistochemical staining, the CXCL12 protein mainly located in the normal pancreatic cell envelopes and/or cytolymphs. In the immunohistochemical staining, the CXCR4 protein mainly located in the cell envelopes and/or cytolymphs of PAC. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CXCR4 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues (P0.01). The MLVD in PAC were detected by morphometric analysis respectively. The level of MLVD in III-IV stages was higher than I-II stages of PAC (P0.01), and in these cases which had lymphatic metastasis, the level of MLVD significantly increased (P0.01). And there was no correlation between the differentiation and histology types of PAC (P0.05). There was 22 samples that the CXCR4 protein was positive, and among these samples the MLVD was higher than that in negative group of CXCR4 protein (P = 0.003).The expression of CXCR4 was significantly associated with lymphatic metastasis of PAC, and the higher expression of CXCR4 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

AIM: To study the effect of 5-lipoxygenase/cyclooxy-genase-2 (5-LOX/COX-2) dual inhibitor 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 and the effect of DHDMBF30 on human pancreatic cancer in a nude mouse model. METHODS: Investigate the effect of 5-LOX/COX-2 dual inhibitor DHDMBF30 on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 by RT-PCR, MTT assay, FCM and electron microscope. Cell line Capan-2 was inoculated percutaneously on the outer thigh of 12 nude mice. The VEGF mRNA of transplantation tumor was detected by RT-PCR. RESULTS: DHDMBF30 inhibits the proliferation of cell line Capan2, reduces the expression of 5-LOX, COX-2 and VEGF. After Capan2 was treated with DHDMBF30, we found that the apoptosis peak of the experimental group was significantly higher than that of the contrast group (3.08 ± 1.89 vs 27.67 ± 0.52, P < 0.001). The tumor weight of the DHDMBF30 group was significantly lower than PBS control groups (1.35 ± 0.47 vs 2.92 ± 0.73, P < 0.01). Expression of VEGF in the DHDMBF30 group was significantly decreased. CONCLUSION: DHDMBF30 inhibits the proliferation of the pancreatic cell line Capan2, and induces apoptosis and inhibits the growth of pancreatic cancer in nude mice.