TY - JOUR
T1 - Interaction of plasminogen-related protein B with endothelial and smooth muscle cells in vitro
AU - Morioka, Hideo
AU - Morii, Takeshi
AU - Vogel, Tikva
AU - Hornicek, Francis J.
AU - Weissbach, Lawrence
N1 - Funding Information:
This work was supported in part by a grant from the Elsa U. Pardee Foundation, by Bio-Technology General Corporation (Rehovot, Israel), and by a generous endowment from Harry Wechsler. H.M. is a recipient of the 2000 Award for Research Fellowship from the Nakayama Foundation for Human Science of Japan.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Plasminogen-related protein B (PRP-B) closely resembles the N-terminal plasminogen activation peptide, which is released from plasminogen during conversion to plasmin. We have previously demonstrated that the steady-state level of mRNA encoding PRP-B is increased within tumor tissues, and that recombinant PRP-B antagonizes neoplastic growth when administered systemically to mice harboring tumors, but no insights into the cell targets of PRP-B have been presented. Employing serum-free medium optimized for culturing human endothelial or smooth muscle cells, we show that recombinant PRP-B inhibits basic fibroblast growth factor-dependent cell migration for both cell types, as well as tube formation of endothelial cells. Comparison with the angiogenesis inhibitors angiostatin and endostatin revealed similar results. Recombinant PRP-B is effective in promoting cell attachment of endothelial and smooth muscle cells, and antibody interference experiments reveal that the interaction of recombinant PRP-B with endothelial cells is mediated at least in part by αv-containing integrins. Inhibition of angiogenesis in vivo by PRP-B was demonstrated in the chicken chorioallantoic membrane assay. PRP-B and other antiangiogenic molecules may elicit metabolic perturbations in endothelial cells as well as perivascular mesenchymal cells such as smooth muscle cells and pericytes.
AB - Plasminogen-related protein B (PRP-B) closely resembles the N-terminal plasminogen activation peptide, which is released from plasminogen during conversion to plasmin. We have previously demonstrated that the steady-state level of mRNA encoding PRP-B is increased within tumor tissues, and that recombinant PRP-B antagonizes neoplastic growth when administered systemically to mice harboring tumors, but no insights into the cell targets of PRP-B have been presented. Employing serum-free medium optimized for culturing human endothelial or smooth muscle cells, we show that recombinant PRP-B inhibits basic fibroblast growth factor-dependent cell migration for both cell types, as well as tube formation of endothelial cells. Comparison with the angiogenesis inhibitors angiostatin and endostatin revealed similar results. Recombinant PRP-B is effective in promoting cell attachment of endothelial and smooth muscle cells, and antibody interference experiments reveal that the interaction of recombinant PRP-B with endothelial cells is mediated at least in part by αv-containing integrins. Inhibition of angiogenesis in vivo by PRP-B was demonstrated in the chicken chorioallantoic membrane assay. PRP-B and other antiangiogenic molecules may elicit metabolic perturbations in endothelial cells as well as perivascular mesenchymal cells such as smooth muscle cells and pericytes.
KW - Antiangiogenesis
KW - Basic fibroblast growth factor
KW - Endothelial cell
KW - Mural cell
KW - Plasminogen-related protein B
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U2 - 10.1016/S0014-4827(03)00137-X
DO - 10.1016/S0014-4827(03)00137-X
M3 - Article
C2 - 12799192
AN - SCOPUS:0037867605
SN - 0014-4827
VL - 287
SP - 166
EP - 177
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -