CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells.

TitleCD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsWei Q, Zhang F, Richardson MM, Roy NH, Rodgers W, Liu Y, Zhao W, Fu C, Ding Y, Huang C, Chen Y, Sun Y, Ding L, Hu Y, Ma J-X, Boulton ME, Pasula S, Wren JD, Tanaka S, Huang X, Thali M, Hämmerling GJ, Zhang XA
JournalCirculation
Volume130
Issue17
Pagination1493-504
Date Published2014 Oct 21
ISSN1524-4539
KeywordsAnimals, Cell Adhesion Molecules, Cell Line, Cell Movement, Cytoskeleton, Endocytosis, Endothelial Cells, Gangliosides, Hyaluronan Receptors, Kangai-1 Protein, Membrane Microdomains, Mice, Knockout, Neovascularization, Pathologic, Protein Transport, Signal Transduction
Abstract

BACKGROUND: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from inflammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown.

METHODS AND RESULTS: Angiogenesis was examined in Cd82-null mice with in vivo and ex vivo morphogenesis assays. Cellular functions, molecular interactions, and signaling were analyzed in Cd82-null ECs. Angiogenic responses to various stimuli became markedly increased upon Cd82 ablation. Major changes in Cd82-null ECs were enhanced migration and invasion, likely resulting from the upregulated expression of cell adhesion molecules such as CD44 and integrins at the cell surface and subsequently elevated outside-in signaling. Gangliosides, lipid raft clustering, and CD44-membrane microdomain interactions were increased in the plasma membrane of Cd82-null ECs, leading to less clathrin-independent endocytosis and then more surface presence of CD44.

CONCLUSIONS: Our study reveals that CD82 restrains pathological angiogenesis by inhibiting EC movement, that lipid raft clustering and cell adhesion molecule trafficking modulate angiogenic potential, that transmembrane protein modulates lipid rafts, and that the perturbation of CD82-ganglioside-CD44 signaling attenuates pathological angiogenesis.

DOI10.1161/CIRCULATIONAHA.114.011096
Alternate JournalCirculation
PubMed ID25149363
Grant ListCA096991 / CA / NCI NIH HHS / United States
Related Faculty: 
William Rodgers, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700