Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models

Lee, O H; Bae, Soo-Kyung; Bae, Moon‐Kyoung; Lee, Y M; Moon, Eun Joung; J, H; Kwon, Yoo-Wook; Kim, K W

doi:10.1054/bjoc.1999.0931

Cited by 81 publications

(57 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numerous reports indicate that growth factors such as VEGF, bFGF, IGF-I and -II are involved in the angiogenic process in various tumours including breast cancer (Kandel et al, 1991;Grant et al, 1993;Heffelfinger et al, 1999;Neufeld et al, 1999;Lee et al, 2000;Yan et al, 2000). Our results demonstrate that the treatment of MDA-MB-435 oestrogen-independent breast cancers with bombesin/GRP antagonists RC-3095 and RC-3940-II significantly decreased the expression of mRNA for VEGF-A, b-FGF and IGF-II, as well as their protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, there is a significant correlation between activated MMP-2 expression and VEGF expression, and similarly pro-MMP-9 expression tends to correlate with the increment of MVD (Kurizaki et al, 1998). IGF-II has also been described as an angiogenic factor that acts either directly (Volpert et al, 1996;Lee et al, 2000) or indirectly through an increase in VEGF production and the upregulation of the expression of proteolytic enzyme MMP-2 (Kim et al, 1998). Overactive MMPs contribute to an almost complete loss of the peritumoral basement membrane in most cancers including breast carcinoma (Lebeau et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…This complex process involves proteolysis of basement membrane, endothelial cell migration, proliferation and matrix remodelling. Several growth factors such as vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF) and IGF-I and -II contribute either alone or in combination to the secretion of metalloproteinases (MMPs), which results in the degradation of basement membrane in microvessel walls, and the formation of new blood vessels (Kandel et al, 1991;Grant et al, 1993;Neufeld et al, 1999;Lee et al, 2000;Yan et al, 2000). The disruption of the vascular basement membrane may facilitate extravasation of endothelial cells, leading to the formation of neovascular sprouts, as well as intravasation of tumour cells into the vessels.…”

mentioning

confidence: 99%

“…These MMPs may also play a role in tumour vascularisation. Thus, it has been shown that the expression of MMP-2 correlates with VEGF and IGF-II expression, and that of MMP-9 with bFGF and increased microvessel density (MVD) (Kurizaki et al, 1998;Lee et al, 2000).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

et al. 2004

View full text Add to dashboard Cite

The overexpression of angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors (IGFs) plays a role in the migration and proliferation of endothelial cells in many cancers. Consequently, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists on the expression of these angiogenic factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as the vascular density in MDA-MB-435 human oestrogenindependent breast cancers. Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated with bombesin/ GRP antagonists for 6 weeks. Daily administration of 20 mg of RC-3095 or 10 mg of RC-3940-II significantly decreased the weight of MDA-MB-435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was associated with a substantial reduction in the expression of mRNA and protein levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the tumours. Both bombesin/GRP antagonists significantly decreased the vessel density of the tumours by about 37%, as shown by immunohistochemical detection of vessels on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33 -46% reduction in MMP-9 activity after the treatment with either antagonist. In vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC-3940-II, and underscores their possible therapeutic application for treatment of breast cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The conditioned medium containing 5 g secreted proteins was analyzed by gelatin-and casein-based zymographies. 15 The digested area appeared clear on a blue background, indicating the location of matrix metalloproteinase (MMP) activity. To further verify MMP caseinolytic activity, the casein-containing gel was incubated with incubation buffer containing 10 mmol/L EDTA, an inhibitor of MMPs, to observe disappearance of the clear band.…”

Section: Gelatin and Casein Zymographies And Plasminogen Activator Inmentioning

confidence: 99%

Evidence of Human Thrombomodulin Domain as a Novel Angiogenic Factor

Shi

Chang

et al. 2005

Circulation

View full text Add to dashboard Cite

Background-Thrombomodulin is an anticoagulant, endothelial-cell-membrane glycoprotein. A recombinant thrombomodulin domain containing 6 epidermal growth factor-like structures exhibits mitogenic activity. This study explored the novel angiogenic effects of the recombinant domain using in vitro and in vivo models. Methods and Results-Human recombinant thrombomodulin containing 6 epidermal growth factor-like structures (TMD2) and TMD2 plus a serine and threonine-rich domain (TMD23) were prepared using the Pichia pastoris expression system. Combined with purified TMD2 or TMD23, thrombin effectively activated protein C. TMD23 had higher activity than TMD2 in stimulating DNA synthesis in cultured human umbilical vein endothelial cells. Additionally, TMD23 stimulated chemotactic motility and capillarylike tube formation in human umbilical vein endothelial cells, an effect mediated through phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase and the phosphatidylinositol-3 kinase/Akt/endothelial nitric oxide synthase pathway. TMD23 also stimulated endothelial cell expression of matrix metalloproteinases and plasminogen activators, which mediated extracellular proteolysis, leading to endothelial cell invasion and migration during angiogenesis. Furthermore, TMD23-containing implants in rat cornea induced ingrowth of new blood vessels from the limbus. With the murine angiogenesis assay, TMD23 not only induced neovascularization coinjected with Matrigel and heparin but also enhanced angiogenesis in Matrigel containing melanoma A2058 cells in nude mice. Conclusions-The

show abstract

Mitogen activated protein kinase signaling in the kidney: target for intervention?

Borst

Wassef

Kelly

et al. 2006

Signal Transduction

View full text Add to dashboard Cite

Mitogen activated protein kinases (MAPKs) are intracellular signal transduction molecules, which connect cell‐surface receptor signals to intracellular processes. MAPKs regulate a range of cellular activities including cell proliferation, gene expression, apoptosis, cell differentiation and cytokine production. The MAPK superfamily consists of at least four families: extracellular signal‐regulated kinase (ERK), p38 MAPK, Jun‐NH2‐terminal kinase (JNK), and ERK5. Each of these families exerts particular downstream effects, although interactions have been described. MAPK activity is present in the normal kidney. Moreover, in various types of renal disease, renal MAPK expression is increased. Interventions that provide renoprotection, such as ACE‐inhibition or statin therapy, may reduce renal MAPK expression, suggesting that increased renal MAPK expression is involved in the pathophysiology of renal damage. Studies using specific MAPK inhibitors have been used to further elucidate this role. This review gives an overview of available in vitro data on MAPK activation (focussed on renal cell types), and describes MAPK localization and possible functions in the normal and diseased kidney in man, and in experimental renal disease. Studies reporting the effect of conventional renoprotective intervention on renal MAPK expression are reviewed, as well as the available data on specific MAPK inhibition, both in the clinical and experimental setting. The available data appear to support the potential of MAPK inhibition as a novel intervention strategy in renal disease, but future clinical studies are needed to substantiate this assumption, and to establish its safety.

show abstract

Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models

Cited by 81 publications

References 23 publications

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

Evidence of Human Thrombomodulin Domain as a Novel Angiogenic Factor

Mitogen activated protein kinase signaling in the kidney: target for intervention?

Contact Info

Product

Resources

About