Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis—Contribution of New Antibodies for Therapy

Abstract

The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence shows soluble CD146 to be significantly elevated in the serum or interstitial fluid of patients with pathologies related to deregulated angiogenesis, as autoimmune diseases, obstetric and ocular pathologies, and cancers. To block the undesirable effects of this molecule, therapeutic antibodies have been developed. Herein, we review the multifaceted functions of CD146 in physiological and pathological angiogenesis and summarize the interest of using monoclonal antibodies for therapeutic purposes.

CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

“…These results are supported by our study, with pathway analysis of DE serum miRNAs predicting upstream regulation by TGF-β signalling. In other tissues, TGF-β is involved in the regulation of angiogenesis in wound healing, along with CD146, laminins and other basement-membrane-associated proteins [ 78 , 79 ].…”

CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions

“…Results of previous studies have demonstrated that CD146 is not only an adhesion molecule, but also a cellular surface receptor stimulated by miscellaneous ligands, including extracellular matrices and growth factors ( 36 , 37 ). By binding to its corresponding ligands, CD146 closely participates in a number of cell processes, such as proliferation, migration ( 38 ), hypertrophy ( 39 ), angiogenesis ( 40 ) and apoptosis ( 40 , 41 ). CD146 is mostly involved in the development and injury of organs, and the progression of various cancer types to metastases, such as oral cancer, ovarian carcinoma, hepatocellular carcinoma and acute lymphocytic leukemia ( 42 ).…”

MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy

“…Blot-Chabaud and his group identified, in addition to the membrane-anchored form of CD146, a soluble form (sCD146) [20,35,[72][73][74] that is mainly generated by the proteolytic cleavage of the membrane form through metalloproteases [19,35]. As already re- The molecular heterogeneity of the two subpopulations at different stages of melanoma disease and during follow-up also was evident for the floating genes.…”

“…The lgCD146 displays two phosphoryla protein kinase (PKC) and double leucine motifs for baso-lateral membra while the shCD146 isoform contains one PKC and one PDZ-binding domai an involvement in cell signaling [17,18]. In endothelial cells, lgCD146 is dist cell junction and is involved in structural functions, while shCD146 is expres apical pole, contributing to the angiogenetic process [16][17][18][19][20][21][22][23].…”