MAP Kinase (ERK1/2, p38) can be Phosphorylated by Shear Stress Independent of PECAM-1 (CD31) in Vascular Endothelial Cells: PECAM-1 as a Mechanoreceptor

PURPOSE: Mechanical forces, including shear stress (SS), trigger signal transducing events and modulate gene expression in vascular endothelial cells (ECs). However, the primary steps of mechanoreception are still unknown. PECAM-1 (CD31), a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules, is localized to the interendothelial cell adhesion site. PECAM-1 tyrosine phosphorylation has been observed following mechanical stimulation, but the role it plays in mechanosensing in ECs is controversial. The aim of this study was to confirm the involvement of PECAM-1 in ECs signaling cascades in response to SS. METHOD: In this study, PECAM-1 knock-out (KO) and wild-type (WT) rat microvascular ECs, and 50 and 100% confluent bovine aortic ECs (BAECs) were exposed to oscillatory SS (14 dyne/cm2) for 0, 5, 10, 30 or 60 minutes. Activation of the PECAM-1 and the mitogen activated protein (MAP) kinase were assessed by determining the phosphorylation of PECAM-1, extracellular signal-regulated kinase1/2 (ERK1/2) and p38 using immunoprecipitation and immunoblotting. RESULT: The tyrosine-phosphorylation level of PECAM-1 immunoprecipitated from SS-stimulated WT ECs increased. While PECAM-1 was phosphorylated in 100% confluent BAECs, its phosphorylation level in 50% confluent BAECs was not detected by SS. However, ERK1/2 and p38 were also activated by SS in both PECAM-1 KO ECs and 50% confluent BAECs. CONCLUSION: Our results indicate that ERK1/2 and p38 were activated by SS in PECAM-1 KO ECs and 50% confluent BAECs despite no PECAM-1 phosphorylation. This suggests that PECAM-1 can not be a major mechanoreceptor for the activation of MAP kinase in ECs; therefore, other more important mechanoreceptors maybe present in ECs to detect SS and trigger intercellular signal transduction.

Early Gastric Mucosal Cancer Associated with Synchronous Liver Metastasis

Early gastric cancer (EGC) is defined as a carcinoma confined to the mucosa or submucosa of the stomach, with or without lymph-node metastasis. Synchronous liver metastasis is 5~12.8% in advanced gastric cancer, but is very low in EGC. A 64-year-old woman was admitted to St. Vincent's Hospital with a complaint of epigastric pain. Gastrofiberscopic examination showed a polypoid mass on the gastric antrum. Abdominal computed tomography demonstrated an intraluminal polypoid mass in the gastric antrum, but no tumor mass in the liver. A laparotomy revealed a solitary liver metastasis, we performed a distal partial gastrectomy with a group-2 lymph-node dissection and resection of metastatic liver tumor. Histologic examination showed a tubular adenoma with a focal carcinomatous change, which was confined to the gastric mucosa and to the metastatic adenocarcinoma in the liver. We present a case of early gastric mucosal cancer associated with synchronous liver metastasis, along with a review of the literature.