Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites.
Ubiquitous protein kinase CK2 participates in a variety of key cellular functions. We have explored CK2 involvement in angiogenesis. As shown previously, CK2 inhibition reduced endothelial cell proliferation, survival and migration, tube formation, and secondary sprouting on Matrigel. Intraperitoneally administered CK2 inhibitors significantly reduced preretinal neovascularization in a mouse model of proliferative retinopathy. In this model, CK2 inhibitors had an additive effect with somatostatin analog, octreotide, resulting in marked dose reduction for the drug to achieve the same effect. CK2 inhibitors may thus emerge as potent future drugs aimed at inhibiting pathological angiogenesis. Immunostaining of the retina revealed predominant CK2 expression in astrocytes. In human diabetic retinas, mRNA levels of all CK2 subunits decreased, consistent with increased apoptosis. Importantly, a specific CK2 inhibitor prevented recruitment of bone marrow-derived hematopoietic stem cells to areas of retinal neovascularization. This may provide a novel mechanism of action of CK2 inhibitors on newly forming vessels.
Kramerov
A A
AA
Ophthalmology Research Laboratories, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis-2025, Los Angeles, CA 90048, USA. kramerova@cshs.org
Saghizadeh
M
M
Caballero
S
S
Shaw
L C
LC
Li Calzi
S
S
Bretner
M
M
Montenarh
M
M
Pinna
L A
LA
Grant
M B
MB
Ljubimov
A V
AV
D000818:Animals; D000831:Animals, Newborn; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015282:Octreotide / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015861:Retinal Neovascularization / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*
D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II; D015282:Octreotide