Rabbit Anti-Human FN1 (a.a. 2337-2386) Polyclonal antibody

Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO-Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO-Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC-R). GO-Y078 inhibited the growth and mobility of HUVEC-R at 0.75mol/L concentration. Expression analyses by microarray and RT-PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO-Y078. In a knockdown experiment using Si-oligo of fibronectin 1 (FN1), FN1 expression was decreased to half of that in mock experiments as well as GO-Y078. Knockdown of FN1 resulted in the suppression of HUVEC-R growth at 24hours after treatment. Fibronectin is a key molecule contributing to angiogenesis that could be inhibited by GO-Y078. Thus, resistance to vascular endothelial growth factor inhibition can be overcome using GO-Y078.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense stroma, which has a fundamental role in tumor progression. Fibronectin (FN1) is the main constituent of the tumor stroma in pancreatic cancer. This study aimed to explore the association between FN1 and clinicopathological characteristics and disease survival.MethodsFormalin-fixed paraffin-embedded tissue samples from 138 patients with PDAC were constructed into a tissue microarray, followed by immunohistochemical analysis with a recombinant monoclonal FN1 antibody. Chi-square test or Fisher's exact test were used for comparison of FN1 expression and relevant clinicopathological parameters. Kaplan-Meier survival curves and Cox regression analyses were used to assess the association between FN1 and survival.ResultsFN1 was detected in the stromal compartment in most cases (117/138, 84.8%). Compared to the low FN1 expression group, the high FN1 expression group had significantly larger tumor size (P=0.002), more advanced T stage (P=0.039) and N stage (P=0.009), and also worse AJCC stage (P=0.003). However, stromal FN1 expression was not associated with disease-free survival or overall survival.ConclusionsThis study suggests that high stromal FN1 expression is associated with aggressive tumor characteristics in patients with resected PDAC. However, no association between FN1 expression and survival was found.