MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

Research output: Contribution to journalArticle

Prue N. Plummer, Ruth Freeman, Ryan J. Taft, Jelena Vider, Michael Sax, Brittany A. Umer, Dingcheng Gao, Christopher Johns, John S. Mattick, Stephen D. Wilton, Vito Ferro, Nigel A J McMillan, Alexander Swarbrick, Vivek Mittal, Albert S. Mellick

Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.

Original languageEnglish
Pages (from-to)341-352
Number of pages12
JournalCancer Research
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2013

PMID: 22836757

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MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. / Plummer, Prue N.; Freeman, Ruth; Taft, Ryan J.; Vider, Jelena; Sax, Michael; Umer, Brittany A.; Gao, Dingcheng; Johns, Christopher; Mattick, John S.; Wilton, Stephen D.; Ferro, Vito; McMillan, Nigel A J; Swarbrick, Alexander; Mittal, Vivek; Mellick, Albert S.

In: Cancer Research, Vol. 73, No. 1, 01.01.2013, p. 341-352.

Research output: Contribution to journalArticle

Harvard

Plummer, PN, Freeman, R, Taft, RJ, Vider, J, Sax, M, Umer, BA, Gao, D, Johns, C, Mattick, JS, Wilton, SD, Ferro, V, McMillan, NAJ, Swarbrick, A, Mittal, V & Mellick, AS 2013, 'MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells' Cancer Research, vol. 73, no. 1, pp. 341-352. https://doi.org/10.1158/0008-5472.CAN-12-0271

APA

Plummer, P. N., Freeman, R., Taft, R. J., Vider, J., Sax, M., Umer, B. A., ... Mellick, A. S. (2013). MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. Cancer Research, 73(1), 341-352. https://doi.org/10.1158/0008-5472.CAN-12-0271

Vancouver

Plummer PN, Freeman R, Taft RJ, Vider J, Sax M, Umer BA et al. MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. Cancer Research. 2013 Jan 1;73(1):341-352. https://doi.org/10.1158/0008-5472.CAN-12-0271

Author

Plummer, Prue N. ; Freeman, Ruth ; Taft, Ryan J. ; Vider, Jelena ; Sax, Michael ; Umer, Brittany A. ; Gao, Dingcheng ; Johns, Christopher ; Mattick, John S. ; Wilton, Stephen D. ; Ferro, Vito ; McMillan, Nigel A J ; Swarbrick, Alexander ; Mittal, Vivek ; Mellick, Albert S. / MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. In: Cancer Research. 2013 ; Vol. 73, No. 1. pp. 341-352.

BibTeX

@article{51feb7df7f594a12b6f1cb7729f15d18,
title = "MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells",
abstract = "Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.",
author = "Plummer, {Prue N.} and Ruth Freeman and Taft, {Ryan J.} and Jelena Vider and Michael Sax and Umer, {Brittany A.} and Dingcheng Gao and Christopher Johns and Mattick, {John S.} and Wilton, {Stephen D.} and Vito Ferro and McMillan, {Nigel A J} and Alexander Swarbrick and Vivek Mittal and Mellick, {Albert S.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1158/0008-5472.CAN-12-0271",
language = "English",
volume = "73",
pages = "341--352",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "1",

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RIS

TY - JOUR

T1 - MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells

AU - Plummer, Prue N.

AU - Freeman, Ruth

AU - Taft, Ryan J.

AU - Vider, Jelena

AU - Sax, Michael

AU - Umer, Brittany A.

AU - Gao, Dingcheng

AU - Johns, Christopher

AU - Mattick, John S.

AU - Wilton, Stephen D.

AU - Ferro, Vito

AU - McMillan, Nigel A J

AU - Swarbrick, Alexander

AU - Mittal, Vivek

AU - Mellick, Albert S.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.

AB - Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth factor stimulation and show elevated expression in human high-grade breast tumor vasculature. Strikingly, targeting miR-10b and miR-196b led to significant defects in angiogenesis-mediated tumor growth in mice. Targeting these miRNAs may constitute a novel strategy for inhibiting tumor angiogenesis.

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U2 - 10.1158/0008-5472.CAN-12-0271

DO - 10.1158/0008-5472.CAN-12-0271

M3 - Article

VL - 73

SP - 341

EP - 352

JO - Cancer Research

T2 - Cancer Research

JF - Cancer Research

SN - 0008-5472

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ER -

ID: 2493247