Angiogenesis In Pancreatic Adenocarcinoma Research Articles

Computed tomography perfusion imaging evaluation of angiogenesis in patients with pancreatic adenocarcinoma.

BACKGROUNDPancreatic adenocarcinoma is one of the most common malignant tumors of the digestive system. More than 80% of patients with pancreatic adenocarcinoma are not diagnosed until late stage and have distant or local metastases. AIMTo investigate the value of computed tomography (CT) perfusion imaging in the evaluation of angiogenesis in pancreatic adenocarcinoma patients.METHODSThis is a retrospective cohort study. Patients with pancreatic adenocarcinoma and volunteers without pancreatic diseases underwent CT perfusion imaging from December 2014 to August 2017 in Huashan Hospital, Fudan University Shanghai, China.RESULTSA total number of 35 pancreatic adenocarcinoma patients and 33 volunteers were enrolled. The relative blood flow (rBF), and relative blood volume (rBV) were significantly lower in patients with pancreatic adenocarcinoma than in the control group (P < 0.05). Conversely, the relative permeability in patients with pancreatic adenocarcinoma was significantly higher than that in controls (P < 0.05). In addition, rBF, rBV, and the vascular maturity index (VMI) were significantly lower in grade III-IV pancreatic adenocarcinoma than in grade I-II pancreatic adenocarcinoma (P < 0.05). Vascular endothelial growth factor (VEGF), CD105-MVD, CD34-MVD, and angiogenesis rate (AR) were significantly higher in grade III-IV pancreatic adenocarcinoma than in grade I-II pancreatic adenocarcinoma (P < 0.05). Significant correlations between rBF and VEGF, CD105-MVD, AR, and VMI (P < 0.01) were observed. Moreover, the levels of rBV were statistically significantly correlated with those of VEGF, CD105-MVD, CD34-MVD, and VMI (P < 0.01). CONCLUSIONPerfusion CT imaging may be an appropriate approach for quantitative assessment of tumor angiogenesis in pancreatic adenocarcinoma.

Src Regulates Nicotine Induced Inhibitor of DNA-binding Protein Id1 Expression In Pancreatic Adenocarcinoma Cells

Introduction: DNA-binding protein inhibitor Id1 is a helix-loop-helix (HLH) protein which plays a role in cell growth, senescence, and differentiation. Overexpression of Id1 correlates with aggressive phenotypes and tumor progression in several human cancers. Although previous reports have demonstrated that Id1 correlates to tumor angiogenesis in pancreatic adenocarcinoma, the signaling pathways related to these events remains unidentified. Previous reports have demonstrated Src and its family of non-receptor protein tyrosine kinases (SFKs) play a critical role in angiogenesis and tumor progression in pancreatic adenocarcinoma.

Neuropilin-2–Mediated Tumor Growth and Angiogenesis in Pancreatic Adenocarcinoma

Neuropilin-2 (NRP-2) is a coreceptor for vascular endothelial growth factor (VEGF) on endothelial cells. NRP-2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells relative to nonmalignant ductal epithelium. This study determined the role of NRP-2 in PDAC cells. NRP-2 expression was reduced in PDAC cells with stable short-hairpin RNA (shRNA) transfection. Western blotting was done to evaluate signaling intermediates. Migration and invasion studies were carried out in Boyden chambers. Anchorage-independent growth was assessed by soft-agar colony formation. In vivo growth was evaluated using murine subcutaneous and orthotopic xenograft models. Immunohistochemical analysis evaluated in vivo proliferation and angiogenesis. shRNA-NRP-2 decreased NRP-2 levels without affecting neuropilin-1 levels. Akt activation was decreased in clones with reduced NRP-2 (shRNA-NRP-2). shRNA-NRP-2 cells showed decreased migration, invasion, and anchorage-independent growth compared with control cells. In vitro proliferation rates were similar in control- and shRNA-transfected cells. Subcutaneous and orthotopic xenografts from shRNA-transfected cells were significantly smaller than those resulting from control-transfected cells (P < 0.05). Furthermore, shRNA-NRP-2 tumors exhibited less cellular proliferation and decreased microvascular area relative to control tumors (P < 0.05). Constitutive expression of the angiogenic mediator Jagged-1 was reduced in shRNA-NRP-2 cells, whereas vascular endothelial growth factor levels were unchanged. Reduction of NRP-2 expression in PDAC cells decreased survival signaling, migration, invasion, and ability to grow under anchorage-independent conditions. In vivo, reduction of NRP-2 led to decreased growth of xenograft tumors and decreased vascular area, which was associated with decreased Jagged-1 levels. NRP-2 is a potential therapeutic target on PDAC cells.

Expression of vascular endothelial growth factors-C and -D correlate with evidence of lymphangiogenesis and angiogenesis in pancreatic adenocarcinoma

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 effect of SMAD4 expression on angiogenesis of pancreatic adenocarcinoma

Aims: SMAD proteins have been implicated as downstream effectors of TGFβ/BMP signaling. TGFß activates receptors on the cell surface, stimulating the phosphorylation of receptor-regulated SMAD proteins, which then form complexes with SMAD4 that accumulate in the nucleus and activate TGFß responsive gene transcription (e.g. Collagen-I, WAF-1). SMAD4 is inactivated in 50% of the pancreatic adenocarcinomas.