Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors.

Background and study aims: Esophageal squamous papilloma (ESP) is a rare lesion. The aims of this study were to assess the prevalence of ESP in northeastern France and the risk of associated squamous cell carcinoma (SCC). Patients and methods: The charts of 78 patients who were diagnosed with ESP between January 2005 and February 2013 at three hospitals in northeastern France were reviewed. Results: A total of 55 305 endoscopies were performed and 78 ESP were diagnosed (0.01 %). Patients with ESP included 44 males (56.4 %), 34 females (43.6 %); median age 50, interquartile range (IQR) 19 – 86. Median follow-up was 21 months (IQR 0 – 91 mo) and median time between first and second endoscopy was 7 months (IQR 0.5 – 74 mo). Of the total number of patients, 35 (44.9 %) had a second endoscopy. Main endoscopy indication was dyspepsia (24.4 %). Most ESP were isolated (93.6 %) and located at distal esophagus (27 cm, IQR 16 – 40 cm). Median size was 3 mm (IQR 1 – 20 mm). ESP-associated endoscopic lesions were hiatal hernia in 12 patients and esophagitis in 11 patients. Endoscopic treatment was mainly excisional biopsies (60.3 %). Human papillomavirus (HPV) was not detected in the 6 patients with available data. Low dysplasia was found in 2 ESP. During follow-up endoscopies, 2 SCC were detected in 2 different patients; the first SCC was located at the previous resection site of the ESP and the second had a different location. Prevalence of associated cancer was 1.3 %. Conclusion: Prevalence of ESP in northeastern France is similar to that previously reported. Endoscopic findings were also broadly the same as in previous reports. The occurrence of dysplasia and SCC should strongly encourage the endoscopist to totally remove the ESP and to start an endoscopic surveillance, given the potential risk of malignant transformation.

These results underscore an impact of pSTAT3 on the clinical efficacy of anti-EGFR-containing chemotherapy regimens and support the prospective assessment of this biomarker.

Performing CEUS on patients presenting with US findings of acute cholecystitis is relevant, since the presence of a discontinuous or irregular enhancement of the GB wall appears to be correlated with the diagnosis of gangrenous acute cholecystitis.