Insulin-like growth factor binding protein-7 (IGFBP7) blocks vascular endothelial cell growth factor (VEGF)-induced angiogenesis in human vascular endothelial cells

Tamura, Kazuhiro; Hashimoto, Keisuke; Suzuki, Kenta; Yoshie, Mikihiro; Kutsukake, Masahiko; Sakurai, ﻿Toshihiro

doi:10.1016/j.ejphar.2009.01.045

Cited by 79 publications

(75 citation statements)

References 31 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: 83%

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

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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: 83%

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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“…23 Ectopic IGFBP7 expression in cancer cells induces cell senescence and apoptosis by inhibition of AKT1/SMARCB1/SNF5 and BRAF/ MPA2K1/MPARK1 signalling pathways. 24,25 In addition, IGFBP7 has been found to inhibit angiogenesis, by suppressing vascular endothelial growth factor and inducing apoptosis, in human umbilical vein endothelial cells 26 and a mouse melanoma model. 27 Exogenous IGFBP7 repressed glioma cell proliferation via cellular senescence and vessel stabilization in the glioblastoma cell lines U87MG and T98G.…”

Section: Discussionmentioning

confidence: 99%

Low expression of insulin-like growth factor binding protein 7 associated with poor prognosis in human glioma

et al. 2014

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Objectives: To investigate insulin-like growth factor binding protein 7 (IGFBP7) mRNA levels in human glioma and normal brain tissue, and to determine their clinical significance. Methods: In this retrospective study, IGFBP7 mRNA was quantified by real-time reverse transcription-polymerase chain reaction in brain tissue samples from patients with glioma and normal control subjects. Kaplan-Meier and Cox proportional hazards analyses were performed to determine any clinical and prognostic associations. Results: IGFBP7 mRNA levels were significantly lower in glioma tissue (n ¼ 120) than in normal brain tissue (n ¼ 20). Low (i.e. below the median, 5.9) IGFBP7 mRNA levels were significantly associated with larger tumour size (!5 cm, compared with <5 cm, diameter). Patients with high (above median) IGFBP7 had longer overall survival than those with low IGFBP7. Tumour grade and IGFBP7 mRNA level were independent predictors of overall survival. Conclusions: IGFBP7 downregulation is associated with poor prognosis in glioma, and this molecule may represent both a prognostic marker and a potential therapeutic target.

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“…Angiogenesis is essential for tumor development, and increasing evidence shows that IGF-I plays a crucial role in tumor growth by up-regulating the VEGF expression and neovascularization (29). A recent study indicated that IGFBP7 might exhibit angiogenesis-modulating properties, reducing VEGF expression by regulating IGF availability in body fluids and tumor tissues and modulating combination of IGF-I to its receptors (29,30). Moreover, the reduction of VEGF-induced tube formation by IGFBP-7 could be mainly mediated by inhibition of MAP kinase cascade through c-Raf, and BRAF-MEK-ERK signaling (31).…”

Section: Discussionmentioning

confidence: 99%

Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and down-regulating VEGF expression

Ту¹

2010

Oncol Rep

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Abstract. Malignant melanoma (MM) is a type of aggressive skin cancer, and the effective therapy for MM is highly desired. Recently, genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP-7) is a critical step in development of MM, and this secreted protein plays a central role in apoptosis of MM. Furthermore, a prostatic carcinoma cell line stably transfected with IGFBP-7 cDNA showed poor tumorigenicity. Thus, we supposed it to be an efficacious agent for inhibiting melanomas. In this study, we constructed pEGFC1-IGFBP7 to try to obtain high expression of IGFPB7 and then we demonstrated that this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vitro. Moreover, intratumoral injection of pEGFC1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth is due to apoptosis and reduced expression of VEGF induced by pEGFC1-IGFBP7. These results suggest a potential new clinical strategy for MM treatment.

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Insulin-like growth factor binding protein-7 (IGFBP7) blocks vascular endothelial cell growth factor (VEGF)-induced angiogenesis in human vascular endothelial cells

Cited by 79 publications

References 31 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

Low expression of insulin-like growth factor binding protein 7 associated with poor prognosis in human glioma

Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and down-regulating VEGF expression

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