Galectin-3 interacts with the cell surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

Colomb, F, Wang, W, Simpson, D ORCID: 0000-0002-3962-4895, Zafar, M, Beynon, R ORCID: 0000-0003-0857-495X, Rhodes, JM ORCID: 0000-0002-1302-260X and Yu, LG ORCID: 0000-0001-9641-3712 (2017) Galectin-3 interacts with the cell surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells. Journal of Biological Chemistry, 292 (20). pp. 8381-8389.

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Official URL: https://www.jbc.org/content/292/20/8381

Abstract

The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.

Item Type:	Article
Uncontrolled Keywords:	carbohydrate-binding protein, cytokine, endothelium, galectin, IL-6, CD146, MCAM, galectin-3
Depositing User:	Symplectic Admin
Date Deposited:	03 Apr 2017 09:38
Last Modified:	19 Jan 2023 07:07
DOI:	10.1074/jbc.M117.783431
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3006768