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Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites

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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.

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The authors thank Dr. Raquel Castellon for in vitro experiments conducted under the NIH grant EY12605 (to AVL), and to Ms. Annette Aoki for excellent technical assistance. Helpful suggestions by Dr. Leon Fine (Cedars-Sinai Medical Center) are gratefully acknowledged. This work is supported by the NIH EY12605 and EY13431 (AVL), EY07739 and EY12601, Juvenile Diabetes Research Foundation International (MBG), Skirball Program in Molecular Ophthalmology, seed grants from the Department of Surgery, Cedars-Sinai Medical Center, Winnick Family Foundation Research Scholar award, and M01 RR00425 (AVL), and grant PBZ-MIN 014/P05/2004 (MB).

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Correspondence to A. A. Kramerov.

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Kramerov, A.A., Saghizadeh, M., Caballero, S. et al. Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites. Mol Cell Biochem 316, 177–186 (2008).

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