Insulin-Like Growth Factor Binding Protein-Related Protein 1 Mediates VEGF-Induced Proliferation, Migration and Tube Formation of Retinal Endothelial Cells

Sun, Tao; Cao, Hui; Xu, Lin; Zhu, Bijun; Gu, Qing; Xu, Xun

doi:10.3109/02713683.2010.545498

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…Anti-angiogenic effects of IGFBP7 have been found in other model systems of cancer. IGFBP7 inhibited VEGF-induced retinal angiogenesis in vitro [24], and it blocked VEGF-induced proliferation of human endothelial cells [25]. Our study is the first to implicate IGFBP7 as having an anti-angiogenic role in the suppression of human breast tumors.…”

Section: Discussionmentioning

confidence: 84%

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

Benatar

Yang

Amemiya

et al. 2011

Breast Cancer Res Treat

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Insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be a tumor suppressor in a variety of cancers. We previously have shown that IGFBP7 expression is inversely correlated with disease progression and poor outcome in breast cancer. Overexpression of IGFBP7 in MDA-MB-468, a triple-negative breast cancer (TNBC) cell line, resulted in inhibition of growth and migration. Xenografted tumors bearing ectopic IGFBP7 expression were significantly growth-impaired compared to IGFBP7-negative controls, which suggested that IGFBP7 treatment could inhibit breast cancer cell growth. To confirm this notion, 14 human patient primary breast tumors were analyzed by qRTPCR for IGFBP7 expression. The TNBC tumors expressed the lowest levels of IGFBP7 expression, which also correlated with higher tumorigenicity in mice. Furthermore, when breast cancer cell lines were treated with IGFBP7, only the TNBC cell lines were growth inhibited. Treatment of NOD/SCID mice harboring xenografts of TNBC cells with IGFBP7 systemically every 3-4 days inhibited tumorigenesis, with associated anti-angiogenic effects, together with increased apoptosis. Upon examining the mechanism of IGFBP7-mediated growth inhibition in TNBC cells, we found that cells not only were arrested in G1 phase of the cell cycle but also underwent senescence as a result of treatment with IGFBP7. Interestingly, IGFBP7 treatment was also associated with strong activation of the stress-associated p38 MAPK pathway, together with upregulation of p53 and the cyclin-dependent protein kinase (CDK) inhibitor, p21(cip1). Prolonged treatment of cells with IGFBP7 resulted in increased cell death, marked by an increase in apoptotic cells and associated cleaved PARP. This is the first study showing that exogenous IGFBP7 inhibits TNBC cell growth both in vitro and in vivo. Taken together, these results suggest IGFBP7 treatment might have therapeutic potential for TNBC.

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Section: Discussionmentioning

confidence: 84%

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

Benatar

Yang

Amemiya

et al. 2011

Breast Cancer Res Treat

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“…37 IGFBP-rp1 has also been shown to inhibit the stimulatory effect of VEGF on retinal endothelial cells in vitro. 38 The elevation of IGFBP-rp1 levels in the aqueous humor of patients with exudative AMD indicates that increased levels of angiogenic factors such as VEGF and IGF-1 work in a complex interplay with antiangiogenic factors to modulate angiogenesis. The increased levels of thrombospondin, an antiangiogenic factor, observed in the AMD group study can be understood similarly.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Aqueous Humor Cytokine Levels Between Patients With Exudative Age-Related Macular Degeneration and Normal Controls

Dong

Woo

Kim

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…The cells demonstrate prolonged expression of VEGF and VEGFRs (19). Due to their ease of culture and rapid transfer, this cell line is widely used in the investigation of PDR and other retina-associated diseases (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Domain I-IV of β2-glycoprotein I inhibits advanced glycation end product-induced angiogenesis by down-regulating vascular endothelial growth factor 2 signaling

Wang

Zhou

Meng

et al. 2014

Molecular Medicine Reports

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Insulin-Like Growth Factor Binding Protein-Related Protein 1 Mediates VEGF-Induced Proliferation, Migration and Tube Formation of Retinal Endothelial Cells

Abstract: IGFBP-rP1 can inhibit the stimulatory effect of VEGF on retinal angiogenesis in vitro by inhibiting expression of B-Raf to induce apoptosis. It is a novel endogenous anti-angiogenic factor with potential therapeutic action in retinal neovascularization dependent disorders.

Cited by 15 publications

References 38 publications

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways

Comparative Analysis of Aqueous Humor Cytokine Levels Between Patients With Exudative Age-Related Macular Degeneration and Normal Controls

Domain I-IV of β2-glycoprotein I inhibits advanced glycation end product-induced angiogenesis by down-regulating vascular endothelial growth factor 2 signaling

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