Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

Abstract

Endoglin (CD105) is an auxiliary receptor of transforming growth factor (TGF)-β family members that is expressed in human melanomas. It is heterogeneously expressed by primary and metastatic melanoma cells, and endoglin targeting as a therapeutic strategy for melanoma tumors is currently been explored. However, its involvement in tumor development and malignancy is not fully understood. Here, we find that endoglin expression correlates with malignancy of primary melanomas and cultured melanoma cell lines. Next, we have analyzed the effect of ectopic endoglin expression on two miRNAs (hsa-mir-214 and hsa-mir-370), both involved in melanoma tumor progression and endoglin regulation. We show that compared with control cells, overexpression of endoglin in the WM-164 melanoma cell line induces; (i) a significant increase of hsa-mir-214 levels in small extracellular vesicles (EVs) as well as an increased trend in cells; and (ii) significantly lower levels of hsa-mir-370 in the EVs fractions, whereas no significant differences were found in cells. As hsa-mir-214 and hsa-mir-370 are not just involved in melanoma tumor progression, but they can also target endoglin-expressing endothelial cells in the tumor vasculature, these results suggest a complex and differential regulatory mechanism involving the intracellular and extracellular signaling of hsa-mir-214 and hsa-mir-370 in melanoma development and progression.

Editorial: Role of membrane-bound and circulating endoglin in disease

“…Some of these studies have tested the endoglin neutralizing antibody TRC105 (Carotuximab ® , Tracon Pharmaceuticals, San Diego, CA, USA), mostly in the context of anti-angiogenic therapies, using a wide variety of preclinical cancer models as well as phase I-III clinical studies of cancer patients ( 23 , 24 ). Additional studies of cancer development have analyzed the role of endoglin in tumor cells themselves ( 26 ). Hakuno et al analyzed the expression of endoglin in three types of human squamous cell carcinoma (SCC): head and neck (HNSCC), esophageal (ESCC), and vulvar (VSCC) cancers.…”