Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma

Negar Babae; Meriem Bourajjaj; Yijia Liu; Judy R Van Beijnum; Francesco Cerisoli; Puthupparampil V Scaria; Mark Verheul; Maaike P Van Berkel; Ebel H E Pieters; Rick J Van Haastert; Afrouz Yousefi; Enrico Mastrobattista; Gert Storm; Eugene Berezikov; Edwin Cuppen; Martin Woodle; Roel Q J Schaapveld; Gregoire P Prevost; Arjan W Griffioen; Paula I Van Noort; Raymond M Schiffelers

Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma

Negar Babae, Meriem Bourajjaj, Yijia Liu, Judy R Van Beijnum, Francesco Cerisoli, Puthupparampil V Scaria, Mark Verheul, Maaike P Van Berkel, Ebel H E Pieters, Rick J Van Haastert, Afrouz Yousefi, Enrico Mastrobattista, Gert Storm, Eugene Berezikov, Edwin Cuppen, Martin Woodle, Roel Q J Schaapveld, Gregoire P Prevost, Arjan W Griffioen, Paula I Van NoortRaymond M Schiffelers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

108 Citations (Scopus)

Abstract

Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.

Original language	English
Pages (from-to)	6687-700
Number of pages	14
Journal	Oncotarget
Volume	5
Issue number	16
Publication status	Published - 30 Aug 2014

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Babae, N., Bourajjaj, M., Liu, Y., Van Beijnum, J. R., Cerisoli, F., Scaria, P. V., Verheul, M., Van Berkel, M. P., Pieters, E. H. E., Van Haastert, R. J., Yousefi, A., Mastrobattista, E., Storm, G., Berezikov, E., Cuppen, E., Woodle, M., Schaapveld, R. Q. J., Prevost, G. P., Griffioen, A. W., ... Schiffelers, R. M. (2014). Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget, 5(16), 6687-700.

@article{d81f3630a0ad41de8c75fb92ca4a18ca,

title = "Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma",

abstract = "Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.",

author = "Negar Babae and Meriem Bourajjaj and Yijia Liu and {Van Beijnum}, {Judy R} and Francesco Cerisoli and Scaria, {Puthupparampil V} and Mark Verheul and {Van Berkel}, {Maaike P} and Pieters, {Ebel H E} and {Van Haastert}, {Rick J} and Afrouz Yousefi and Enrico Mastrobattista and Gert Storm and Eugene Berezikov and Edwin Cuppen and Martin Woodle and Schaapveld, {Roel Q J} and Prevost, {Gregoire P} and Griffioen, {Arjan W} and {Van Noort}, {Paula I} and Schiffelers, {Raymond M}",

year = "2014",

month = aug,

day = "30",

language = "English",

volume = "5",

pages = "6687--700",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals",

number = "16",

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Babae, N, Bourajjaj, M, Liu, Y, Van Beijnum, JR, Cerisoli, F, Scaria, PV, Verheul, M, Van Berkel, MP, Pieters, EHE, Van Haastert, RJ, Yousefi, A, Mastrobattista, E, Storm, G, Berezikov, E, Cuppen, E, Woodle, M, Schaapveld, RQJ, Prevost, GP, Griffioen, AW, Van Noort, PI & Schiffelers, RM 2014, 'Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma', Oncotarget, vol. 5, no. 16, pp. 6687-700.

TY - JOUR

T1 - Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma

AU - Babae, Negar

AU - Bourajjaj, Meriem

AU - Liu, Yijia

AU - Van Beijnum, Judy R

AU - Cerisoli, Francesco

AU - Scaria, Puthupparampil V

AU - Verheul, Mark

AU - Van Berkel, Maaike P

AU - Pieters, Ebel H E

AU - Van Haastert, Rick J

AU - Yousefi, Afrouz

AU - Mastrobattista, Enrico

AU - Storm, Gert

AU - Berezikov, Eugene

AU - Cuppen, Edwin

AU - Woodle, Martin

AU - Schaapveld, Roel Q J

AU - Prevost, Gregoire P

AU - Griffioen, Arjan W

AU - Van Noort, Paula I

AU - Schiffelers, Raymond M

PY - 2014/8/30

Y1 - 2014/8/30

N2 - Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.

AB - Tumor-angiogenesis is the multi-factorial process of sprouting of endothelial cells (EC) into micro-vessels to provide tumor cells with nutrients and oxygen. To explore miRNAs as therapeutic angiogenesis-inhibitors, we performed a functional screen to identify miRNAs that are able to decrease EC viability. We identified miRNA-7 (miR-7) as a potent negative regulator of angiogenesis. Introduction of miR-7 in EC resulted in strongly reduced cell viability, tube formation, sprouting and migration. Application of miR-7 in the chick chorioallantoic membrane assay led to a profound reduction of vascularization, similar to anti-angiogenic drug sunitinib. Local administration of miR-7 in an in vivo murine neuroblastoma tumor model significantly inhibited angiogenesis and tumor growth. Finally, systemic administration of miR-7 using a novel integrin-targeted biodegradable polymeric nanoparticles that targets both EC and tumor cells, strongly reduced angiogenesis and tumor proliferation in mice with human glioblastoma xenografts. Transcriptome analysis of miR-7 transfected EC in combination with in silico target prediction resulted in the identification of OGT as novel target gene of miR-7. Our study provides a comprehensive validation of miR-7 as novel anti-angiogenic therapeutic miRNA that can be systemically delivered to both EC and tumor cells and offers promise for miR-7 as novel anti-tumor therapeutic.

M3 - Article

C2 - 25149532

SN - 1949-2553

VL - 5

SP - 6687

EP - 6700

JO - Oncotarget

JF - Oncotarget

IS - 16

ER -

Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma

Abstract

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