**MCAM and its Isoforms as Novel Targets in Angiogenesis Research and Therapy Angiogenesis Research and Therapy**

**MCAM and its Isoforms as Novel Targets in** 

Jimmy Stalin, Lucie Vivancos, Nathalie Bardin, Françoise Dignat-George and Marcel Blot-Chabaud Nathalie Bardin, Françoise Dignat-George and Marcel Blot-Chabaud

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66765

Jimmy Stalin, Lucie Vivancos,

#### **Abstract**

Melanoma cell adhesion molecule (MCAM) (CD146) is a membrane glycoprotein of the mucin family. It is one of the numerous proteins composing the junction of the vascular endothelium, and it is expressed in other cell types such as cancer cells, smooth muscle cells, and pericytes. Some recent works were designed to highlight its structural features, its location in the endothelium, and its role in angiogenesis, vascular permeability, and monocyte transmigration, but also in the maintenance of endothelial junctions and tumor development. MCAM exists in different splice variants and is shedded from the vascular membrane by metalloproteases. Studies about MCAM spliced and cleaved variant on human angiogenic physiological and pathological models permit a better understanding on the roles initially described for this protein. Furthermore, this knowledge will help in the future to develop therapeutic and diagnostic tools targeting specifically the different MCAM variant. Recent advances in research on angiogenesis and in the implication of MCAM in this process are discussed in this chapter.

**Keywords:** angiogenesis, MCAM (CD146), melanoma, physiology, pathology

## **1. Introduction**

Angiogenesis is the process of new blood vessel formation from preexisting vessels. It contributes to physiological processes such as development and wound healing, but also to pathological processes, such as tumor angiogenesis. The identification of new targets involved in angiogenesis remains an important challenge to fully understand the involved mechanisms and to generate new therapeutic tools. Recent studies have highlighted CD146, an endothelial junctional molecule, as a key factor in angiogenesis. This molecule that displays different

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

isoforms and that is present on different cell types could hence constitute a novel target for therapy. Different reviews have underlined its structural features, localization, and functions in the endothelium. This chapter thus mainly addresses the differences in CD146 isoforms with a special focus on their role in angiogenesis and the therapeutic tools targeting the molecule.

Historically, CD146 was discovered in 1987 by Professor J.P. Jonhson for the first time. It was identified as a marker of melanoma progression. These data were obtained by using an antibody generated by mouse immunization with a cell lysate of metastasizing melanoma. This antibody (MUC18) allowed the identification of a 113 kDa transmembrane protein. MCAM (melanoma cell adhesion molecule) described as a marker of metastasizing melanoma [1].

In 1991, the team of Professor. F. Dignat-George identified Sendo-1 antigen as a marker of circulating endothelial cells in the blood by flow cytometry. This was made possible through the generation of a mouse monoclonal antibody named Sendo -1 [2] obtained by mice immunization with a HUVEC cell lysate. Sendo-1 was able to stain the human endothelium whatever the vessel size and its anatomical location within the vascular tree [3, 4]. Gicerin and HEMCAM refer both to the avian homologues of the molecule [5].

As reported in Kobé in 1997, CD146 (cluster of differentiation 146) is now the official name grouping Sendo-1/MUC18/MCAM/gicerin/HEMCAM (Sendo-MUC18 preCD, Workshop Report).
