Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen

Colman, Robert W.; Pixley, Robin A.; Sáinz, Irma M.; Song, Jakyoung; Isordia‐Salas, Irma; Muhamed, S. N.; Powell, John; Mousa, Shaker A.

doi:10.1046/j.1538-7836.2003.00025.x

Cited by 65 publications

(63 citation statements)

References 34 publications

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“…Previous studies (6,10,31) have shown that HKa at nanomolar concentrations inhibits cell proliferation and adhesion and induces apoptosis of endothelial cells in the presence of Zn 2ϩ . Recombinant domain 5 of HKa (GST-D5) partly resembles these effects of HKa, indicating that D5 is likely the active domain responsible for the antiangiogenic activity of HKa.…”

Section: Discussionmentioning

confidence: 95%

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Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecular-weight kininogen

Wang

Hasham

Isordia‐Salas

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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We (8) reported that the cleaved high-molecular-weight kininogen (HKa) and its domain 5 (D5) inhibited angiogenesis. Further studies (15) revealed that D5 could inhibit cell proliferation and induce apoptosis of proliferating endothelial cells, which together may represent a critical part of antiangiogenic activity of HKa and D5. In the present study, we further examined the effect of HKa on cell cycle progression and cell viability. We report that HKa induced a significant upregulation of Cdc2 and cyclin A in proliferating endothelial cells, concurrent with a marked increase of Cdc2 activity. The increased expression of Cdc2 and cyclin A by HKa was not associated with an apparent change in cell cycle profiles of basic fibroblast growth factor-stimulated proliferating cells, but closely correlated with a marked increase of apoptosis, suggesting that the elevated Cdc2 activity is involved in HKa-induced apoptosis of proliferating endothelial cells. Our results support an emerging hypothesis that Cdc2 and cyclin A are important regulators for cell cycle as well as for apoptosis.

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Section: Discussionmentioning

confidence: 95%

“…These findings represent a novel biological function of this molecule. Interestingly, it has recently been demonstrated that bradykinin stimulates angiogenesis (10,21,24). Therefore, HK is a precursor of both an angiogenic stimulator (bradykinin) and an inhibitor (HKa).…”

mentioning

confidence: 99%

Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecular-weight kininogen

Wang

Hasham

Isordia‐Salas

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Intact HK, which under most physiologic circumstances is in molar excess to HKa, is likely to inhibit HKa binding to uPAR under physiological conditions (24 -26). Bradykinin liberated from HK expresses pro-angiogenic activity (26,27). Thus, it is likely that HKa inhibits angiogenesis only in situations where sufficiently large concentrations of these proteolytic fragments have been generated to overcome the competing influence of native plasma HK.…”

Section: Discussionmentioning

confidence: 99%

Mapping the Interaction between High Molecular Mass Kininogen and the Urokinase Plasminogen Activator Receptor

Mahdi

Shariat‐Madar

Kuo

et al. 2004

Journal of Biological Chemistry

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The urokinase plasminogen activator receptor (uPAR) is a multifunctional, GPI-linked receptor that modulates cell adhesion/migration and fibrinolysis. We mapped the interaction sites between soluble uPAR (su-PAR) and high molecular mass kininogen (HK). Binding of biotin-HK to suPAR was inhibited by HK, 56HKa, and 46HKa with an IC 50 of 60, 110, and 8 nM, respectively. We identified two suPAR-binding sites, a higher affinity site in the light chain of HK and 46HKa (His 477 -Gly 496 ) and a lower affinity site within the heavy chain (Cys 333 -Lys 345 ). HK predominantly bound to suPAR fragments containing domains 2 and 3 (S-D2D3). Binding of HK to domain 1 (S-D1) was also detected, and the addition of S-D1 to S-D2D3 completely inhibited biotin-HK or -46HKa binding to suPAR. Recent investigations indicate that high molecular mass kininogen (HK)1 binds to endothelial cell membranes through an interaction with a multiprotein receptor complex comprising at least cytokeratin 1, gC1qR, and the urokinase plasminogen activator receptor (uPAR) (1-5). The three proteins co-localize on the endothelial cell membrane (6). The same three proteins form a receptor complex for factor XII (7), but binding of factor XII in vivo is likely limited both by the low plasma concentration of free Zn 2ϩ , which is below the requirement for FXII binding and by the much higher plasma concentration of HK (7). Binding of HK to this multiprotein receptor complex predominates, localizing prekallikrein (PK) to the cell surface. The plasma concentration of PK and the ambient free Zn 2ϩ concentration in plasma also prevent FXI from binding to HK under conditions where platelets or other cells are not activated (8). PK bound to HK on endothelial cells is proteolyzed by membrane-expressed prolylcarboxypeptidase to form plasma kallikrein (9, 10). This multiprotein receptor complex thereby regulates the assembly and activation of the plasma kallikrein/ kinin system.The requirements for HK binding to each component of this receptor complex and the effects of other biologically relevant ligands, e.g. urokinase, on this binding have not been well delineated. It is known that both the heavy and light chains of HK interact with a region of cytokeratin 1 coded by exon 1 (2). Antibody to this region completely inhibits HK binding to cytokeratin 1 as well as to the receptor complex (6). Likewise, some antibodies to gC1qR and uPAR completely block HK binding to the proteins individually as well as when they are part of the complex expressed on endothelial cells (6, 8). However, it is unclear whether each component of the cellular complex recognizes discrete or overlapping portions of HK and whether each molecule of HK binds to more than one component of the complex at the same time. To begin to address these issues, we sought to identify the regions in HK and uPAR required for binding. The results indicate the existence of multiple potential sites of interaction between this ligand and receptor and provide insight into the assembly of HK on its multireceptor co...

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“…Chick Chorioallantoic Membrane Assay Chick chorioallantoic membrane (CAM) assays were done according to previously published methods (16,17). The surfaces of 10-d-old post-fertilization chick eggs were sterilized and the CAM exposed by cutting a window (1 cm 2 ) on one side of the egg using the false air sac technique.…”

Section: Methodsmentioning

confidence: 99%

Enhancement of vascular endothelial growth factor–mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression

Kim

Choi

Yang

et al. 2009

Molecular Cancer Therapeutics

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Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen

Cited by 65 publications

References 34 publications

Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecular-weight kininogen

Upregulation of Cdc2 and cyclin A during apoptosis of endothelial cells induced by cleaved high-molecular-weight kininogen

Mapping the Interaction between High Molecular Mass Kininogen and the Urokinase Plasminogen Activator Receptor

Enhancement of vascular endothelial growth factor–mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression

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