Inhibition of angiogenesis by extracellular protein kinase A.
The cyclic-AMP dependent protein kinase (PKA) signaling pathway regulates cell growth, development, metabolism, and gene expression. Peripheral blood of cancer patients but not normal individuals, shows increased catalytic subunit levels of PKA (PKAc). We showed here that this extracellular form of PKAc (ECPKA) from conditioned media of cultured cancer cells as well as purified PKAc inhibit angiogenesis, using the in utero chicken embryo chorioallantoic membrane assay. Inhibition of angiogenesis is partially reversed by PKI, a peptide inhibitor of PKA, thus suggesting an anti-angiogenic role for ECPKA. The significance of ECPKA in cancer is discussed.
Department of Medicine, The University of Toledo College of Medicine, Toledo, OH 43614, USA.
Maria
M
Szkudlarek
Rual M
RM
Bosio
Qiong
Q
Wu
Khew-Voon
KV
Chin
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002642:Chick Embryo; D017077:Culture Media, Conditioned; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000201:enzymology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*
D017077:Culture Media, Conditioned; D017868:Cyclic AMP-Dependent Protein Kinases