Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 marker, a novel angiogenesis marker

Abstract

Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), an orphan adhesion G-protein coupled receptor, was reported as a regulator of angiogenesis, also involved in cancer progression and development. More recently, ELTD1 was identified as a potential new tumor marker for high-grade glioma. ELTD1, belongs to the G-protein coupled receptor superfamily that comprises the biggest receptor family in the human genome. Following the discovery of ELTD1 almost a decade ago, only a few research groups have attempted to find its role in normal and tumor cells, important information about this receptor remaining still unknown. The ELTD1 ligand has not currently been identified and intracellular signaling studies have not yet been performed in normal or tumor cells. Although the current published data on ELTD1 function and structure are rather limited, this receptor seems to be very important, not only as biomarker, but also as molecular target in glioblastoma. This review summarizes and discusses the current knowledge on ELTD1 structure, function, and its role in both physiological and tumoral angiogenesis.

Keywords: ELTD1; angiogenesis; biomarker; glioma.

Figure 1

Structure of the ELTD1 receptor. The VEGF/bFGF signaling pathway has a positive effect on ELTD1 expression, while DLL4/Notch pathway determines a reduction in protein expression.– Abbreviations: ELTD1, epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1; VEGF, vascular epithelial growth factor; FGF, fibroblast growth factor; DLL4, delta-like ligand 4; GPS, G-protein coupled protein hormone receptor proteolysis site.

Figure 2

ELTD1 gene expression in tissues, organs, or cell lines in the 1,418,058 (A) and 1,418,059 (B) databases. The samples were obtained from mice. Data were obtained from the Biogps online database (http://biogps.org/#goto=genereport&id=170,757, accessed October 17, 2015). Results are represented as the 20 most highly expressed gene levels for each probe in order to highlight the most relevant data. Abbreviation: ELTD1, epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1.

Figure 3

ELTD1 protein levels in human cancer cell lines. The results show the intensity of antibody staining (protein levels) for each cell line. Results were obtained from the Human Protein Atlas Database (http://www.proteinatlas.org/ENSG00000162618-ELTD1/cell/HPA025229, accessed October 17, 2015). Abbreviation: ELTD1, epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1.

Figure 4

ELTD1 genetic alterations (mutations, amplifications, and deletions) in different human tumor samples. Results are shown as the number of alterations and percentage of alterations per samples analyzed in each individual study and only shows cancer types where genetic alterations are present. The results were obtained from the BioPortal for Cancer Genomics database (http://bit.ly/1PyuYcR, accessed October 17, 2015). Abbreviations: ELTD1, epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1; lung SC, lung squamous cells.