Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium

Abstract

Vascular endothelial cells (EC) play a key role in a variety of pathophysiologic processes, such as angiogenesis, inflammation, cancer metastasis, and vascular diseases. As part of a strategy to identify all genes expressed in human EC, a full-length cDNA encoding a potential secreted protein harboring 10 epidermal growth factor (EGF)-like domains and one CUB domain at the carboxyl terminus (termed, SCUBE1 for Signal peptide-CUB-EGF-like domain containing protein 1) was identified. SCUBE1 shares homology with several protein families, including members of the fibrillin and Notch families, and the anticoagulant proteins, thrombomodulin and protein C. SCUBE1 mRNA is found in several highly vascularized tissues such as liver, kidney, lung, spleen, and brain and is selectively expressed in EC by in situ hybridization. SCUBE1 is a secreted glycoprotein that can form oligomers and manifests a stable association with the cell surface. A second gene encoding a homologue (designated SCUBE2) was also identified and is expressed in EC as well as other cell types. SCUBE2 is also a cell-surface protein and can form a heteromeric complex with SCUBE1. Both SCUBE1 and SCUBE2 are rapidly down-regulated in EC after interleukin-1␤ and tumor necrosis factor-␣ treatment in vitro and after lipopolysaccharide injection in vivo. Thus, SCUBE1 and SCUBE2 define an emerging family of human secreted proteins that are expressed in vascular endothelium and may play important roles in development, inflammation, and thrombosis.

Identification and validation of an ERBB2 gene expression signature in breast cancers

“…Moreover, an interplay between ERBB2 and ER pathways has been demonstrated (Pietras et al, 1995). There were also SCUBE2, a gene encoding a secreted protein with an EGF-like domain (Yang et al, 2002), and CELSR2, which encodes a nonclassical cadherin. These two molecules might have antagonistic regulatory roles of ERBB2 activities at the cell membrane.…”

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

“…The SCUBE gene family has been shown to be expressed in the gonads, central nervous system and limb buds during mouse embryogenesis (Grimmond et al 2000). SCUBE perform highly important role during organogenesis and branching morphogenesis (Yang et al 2002). SCUBE1 levels have been shown to increase in inflammation and hypoxia, conditions resulting in angiogenesis in osteoblasts and bones (Yang et al 2002).…”

“…SCUBE perform highly important role during organogenesis and branching morphogenesis (Yang et al 2002). SCUBE1 levels have been shown to increase in inflammation and hypoxia, conditions resulting in angiogenesis in osteoblasts and bones (Yang et al 2002). SCUBE is associated with inflammation and hypoxia-related diseases (Dai et al 2008).…”

New Gene Profiling in Determination of Breast Cancer Recurrence and Prognosis in Iranian Women

“…SCUBE2 is linked to the expression of estrogen receptor α (ERα). Searching for effective molecular markers is necessary to predict the disease course and guide treatment decision (Yang et al, 2002;Brennan and Gallagher, 2008). SCUBE2 is expressed in endothelium, fibroblasts, and renal mesangial cells (Yang et al, 2002;Fan et al, 2006).…”