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The C-type lectin domain (CTLD) group 14 family of transmembrane glycoproteins consist of thrombomodulin, CD93, CLEC14A and CD248 (endosialin or tumour endothelial marker-1). These cell surface proteins exhibit similar ectodomain architecture and yet mediate a diverse range of cellular functions, including but not restricted to angiogenesis, inflammation and cell adhesion. Thrombomodulin, CD93 and CLEC14A can be expressed by endothelial cells, whereas CD248 is expressed by vasculature associated pericytes, activated fibroblasts and tumour cells among other cell types. In this article, we review the current literature of these family members including their expression profiles, interacting partners, as well as established and speculated functions. We focus primarily on their roles in the vasculature and inflammation as well as their contributions to tumour immunology. The CTLD group 14 family shares several characteristic features including their ability to be proteolytically cleaved and engagement of some shared extracellular matrix ligands. Each family member has strong links to tumour development and in particular CD93, CLEC14A and CD248 have been proposed as attractive candidate targets for cancer therapy.
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http://dx.doi.org/10.1111/febs.14985 | DOI Listing |
Angiogenesis
May 2024
Department of Surgery, University of Colorado Anschutz Medical Campus, 12800 E 19th Avenue, RC1-North, P18-8116, Aurora, CO, 80045, USA.
C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology.
View Article and Find Full Text PDFInt J Mol Sci
May 2023
Unité de Recherche en Pharmaco-Immunologie (EPI), Université et CHU de La Réunion, 97400 Saint-Denis, France.
CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester).
View Article and Find Full Text PDFBMC Genomics
June 2022
Department of Life Sciences, University of Siena, Siena, Italy.
Background: The group XIV of C-type lectin domain-containing proteins (CTLDcps) is one of the seventeen groups of CTLDcps discovered in mammals and composed by four members: CD93, Clec14A, CD248 and Thrombomodulin, which have shown to be important players in cancer and vascular biology. Although these proteins belong to the same family, their phylogenetic relationship has never been dissected. To resolve their evolution and characterize their protein domain composition we investigated CTLDcp genes in gnathostomes and cyclostomes and, by means of phylogenetic approaches as well as synteny analyses, we inferred an evolutionary scheme that attempts to unravel their evolution in modern vertebrates.
View Article and Find Full Text PDFDifferentiation
January 2022
CNRS UMI 2820, Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan; Université de technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de recherche Royallieu CS 60319, 60203, Compiègne Cedex, France. Electronic address:
Oncol Lett
October 2019
Institute of Life Sciences, Bhubaneswar, Odisha 751023, India.
The growth and metastasis of tumors is dependent on angiogenesis. C-type lectins are carbohydrate-binding proteins with a diverse range of functions. The C-type lectin family XIV members are transmembrane glycoproteins, and all four members of this family have been reported to regulate angiogenesis, although the detailed mechanism of action has yet to be completely elucidated.
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