Abstract 1014: Semaphorin 4D involves in the regulation of cell motility through its receptor Plexin B1 in pancreatic cancer

Abstract

Abstract Introduction: Semaphorins are a large family of either membrane-bound or secreted proteins that provide axonal guidance in neuronal tissues and regulate cell motility in many types of cells. Recent articles reported that Semaphorin 4D (Sema 4D) enhanced in vitro motility and invasiveness through its receptor Plexin B1 and Met, and increased in vivo metastasis potential in breast cancer. However, these expression and function in pancreatic cancer is not known. Purpose: In the present study, we investigated the clinicopathological significance of Sema 4D and Plexin B1 expression in surgically resected pancreatic ductal adenocarcinoma sections and the regulation of cell motility through the Sema 4D - Plexin B1 signaling pathway. Material & Methods: The mRNA expression level of Sema 4D and Plexin B1 were evaluated by Quantitative Real Time PCR from 12 surgical specimens and 10 normal pancreatic tissues. Expression of Sema 4D and Plexin B1 were also evaluated immunohistochemically from 90 patients. Using pancreatic cancer cell lines, the expression of endogenous Plexin B1 and Met protein was investigated by western blotting. And the phosphorylation of Met protein after stimulating by Sema4D was evaluated. As functional analysis, scratch assay and MTT assay were carried out. Results: The mRNA expression level of Sema 4D and Plexin B1 were significantly high in cancer tissues compared to normal pancreas tissues. Immunostaining showed that Sema 4D strongly expressed in lymphocytes and macrophages, as previously reported. Ninety two percent (83 out of 90 cases) pancreatic cancer samples overexpressed Plexin B1 compared to normal pancreas tissues. Endogenous Plexin B1 and Met protein were detected in eight pancreatic cancer cell lines, with a variety of expression levels. Sema 4D stimulation activated Met protein, and significantly induced cell migration. Discussion: Here we show that Sema 4D involves in the regulation of cell motility through its receptor Plexin B1. And the results of immunostaining suggest that Sema 4D could play a role in the interaction between tumor cells and tumor microenvironment in pancreatic cancer tissues. As many attempts are now ongoing to target the tumor stroma, these findings provide a new insight into molecular targeted therapies for pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1014.