Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay

Ley, Carsten Dan; Olsen, Minna W.B.; Lund, Eva Løbner; Kristjansen, Paul E.G.

doi:10.1016/j.mvr.2004.06.002

Cited by 54 publications

(33 citation statements)

References 26 publications

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“…25 Therefore, various factors and their complicated interplay seemed to be essential. Indeed, in some previous reports, superior results for angiogenesis have been obtained through the application of multiple factors than through the introduction of a single factor, eg, paired combinations of bFGF and PDGF, 26,27 VEGF and bFGF, 28,29 VEGF and PDGF, 30 or PDGF and TGF-␤, 31 or a triple combination of bFGF, PDGF, and VEGF. 32 Our findings with incomplete AIC with either two or three growth factors suggest that PDGF, EGF, and TGF-␤ contributed to hASC migration and that bFGF played a pivotal role in network formation, although these effects were likely augmented by the synergism of all of the factors.…”

Section: Discussionmentioning

confidence: 99%

Adipose Injury–Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis

Eto

Suga

Inoue

et al. 2011

The American Journal of Pathology

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Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail (AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate the therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor/stromal cells (ASCs) to proliferate, migrate, and form networks compared with vascular endothelial cells, whereas vascular endothelial growth factor did not induce mitogenesis or chemotaxis in human ASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than into other cell types. In ischemic adipose tissues of mice, induced by either a surgical intervention or diabetes, AIC administration enhanced proliferation, especially of CD31 -/CD34 ؉ ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggest that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies regarding morbidity, cost, and physical risks and may be used as an alternative therapy for improving tissue oxygen.

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Section: Discussionmentioning

confidence: 99%

Adipose Injury–Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis

Eto

Suga

Inoue

et al. 2011

The American Journal of Pathology

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“…Embryonic ANG-2 overexpression results in a major disruption of the developing vascular system, suggesting an antagonistic role in angiogenesis (25). Furthermore, it counteracts the angiogenic activity of VEGF and antagonizes the synergistic effect of VEGF with basic fibroblast growth factor in angiogenesis (51,52). In addition, lung and mammary carcinomas that overexpressed ANG-2 and specific induction of ANG-2 in gliomas were found to retard tumor growth and metastasis (42,47).…”

Section: Ang-2mentioning

confidence: 99%

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Shim

Wong

2007

Molecular Cancer Research

150

111

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Angiopoietins (ANG-1 and ANG-2) and their TIE-2 receptor tyrosine kinase have wide-ranging effects on tumor malignancy that includes angiogenesis, inflammation, and vascular extravasation. These multifaceted pathways present a valuable opportunity in developing novel inhibition strategies for cancer treatment. However, the regulatory role of ANG-1 and ANG-2 in tumor angiogenesis remains controversial. There is a complex interplay between complementary yet conflicting roles of both the ANGs in shaping the outcome of angiogenesis. Embryonic vascular development suggests that ANG-1 is crucial in engaging interaction between endothelial and perivascular cells. However, recruitment of perivascular cells by ANG-1 has recently been implicated in its antiangiogenic effect on tumor growth. It is becoming clear that TIE-2 signaling may function in a paracrine and autocrine manner directly on tumor cells because the receptor has been increasingly found in tumor cells. In addition, A 5 B 1 and A v B 5 integrins were recently recognized as functional receptors for ANG-1 and ANG-2. Therefore, both the ligands may have wide-ranging functions in cellular activities that affect overall tumor development. Collectively, these TIE-2 -dependent and TIE-2 -independent activities may account for the conflicting findings of ANG-1 and ANG-2 in tumor angiogenesis. These uncertainties have impeded development of a clear strategy to target this important angiogenic pathway. A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway. (Mol Cancer Res 2007;5(7):655 -65)

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“…Single growth factor stimulation of neoangiogenesis has been disappointing. 17 However, recent work with growth factor combinations-FGF-2 and PDGF-BB, 18 VEGF-A and FGF-2, 19,20 and VEGF-A and PDGF-BB 21 -have shown strong effects in promoting neoangiogenesis. Given the interdependence between angiogenesis and adipogenesis and the potential that efficiently engineered vascularized adipose tissue would have in tissue replacement procedures in breast, trauma, and cancer-related reconstructive procedures, this study explores the potential effect of single and combined therapies of VEGF 120 , PDGF-BB, and FGF-2 on angiogenesis and adipogenesis in an in vivo tissue-engineering model.…”

mentioning

confidence: 99%

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Rophael

Craft

Palmer

et al. 2007

The American Journal of Pathology

120

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De novo tissue generation stimulated by three angiogenic growth factors administered in a factorial design was studied in an in vivo murine tissue engineering chamber. A silicone chamber was implanted around the epigastric pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular endothelial growth factor-120 (VEGF 120 ), recombinant human basic fibroblastic growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF-BB) added as single, double, or triple combinations. Angiogenesis, supporting tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically enhanced by VEGF 120 ؉ FGF-2 (P ‫؍‬ 0.019). FGF-2 (P ‫؍‬ 0.008) and PDGF-BB (P ‫؍‬ 0.01) significantly increased connective tissue/inflammatory cell infiltrate (macrophages, pericytes, and preadipocytes) in double and triple combinations compared with control. At 6 weeks sequential addition of growth factors increased the percent volume of adipose tissue (P < 0.0005, each main effect), with a synergistic increase in adipose tissue in combination treatments (P < 0.0005). Groups containing 300 ng/ml of single growth factors produced significantly less adipose tissue than the triple growth factor combination (P < 0.0005, VEGF 120 and PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations increased early angiogenesis and cell infiltration resulting in synergistically increased adipose tissue growth at 6 weeks. Two way and higher level synergies are likely to be important in therapeutic applications of angiogenic growth factors.

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Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay

Cited by 54 publications

References 26 publications

Adipose Injury–Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis

Adipose Injury–Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

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