Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth

Research output: Contribution to journalArticle

Albert S. Mellick, Prue N. Plummer, Daniel J. Nolan, Dingcheng Gao, Kathryn Bambino, Mary Hahn, Raul Catena, Vivian Turner, Kevin McDonnell, Robert Benezra, Robert Brink, Alexander Swarbrick, Vivek Mittal

Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of a marker that can track EPCs from the BM to tumor neovasculature has impeded progress in understanding the molecular mechanisms underlying EPC biology. Here, we report the use of transgenic mouse and lentiviral models to monitor the BM-derived compartment of the tumor stroma; this approach exploits the selectivity of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced circulating EPCs and yielded significant defects in angiogenesis-mediated tumor growth. Additionally, use of the Id1 proximal promoter to express microRNA-30-based short hairpin RNA inhibited the expression of critical EPC-intrinsic factors, confirming that signaling through vascular endothelial growth factor receptor 2 is required for EPC-mediated tumor biology. By exploiting the selectivity of Id1 gene expression in EPCs, our results establish a strategy to track and target EPCs in vivo, clarifying the significant role that EPCs play in BM-mediated tumor angiogenesis.

Original languageEnglish
Pages (from-to)7273-7282
Number of pages10
JournalCancer Research
Volume70
Issue number18
DOIs
StatePublished - Sep 15 2010

PMID: 20807818

PMCID: PMC3058751

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Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth. / Mellick, Albert S.; Plummer, Prue N.; Nolan, Daniel J.; Gao, Dingcheng; Bambino, Kathryn; Hahn, Mary; Catena, Raul; Turner, Vivian; McDonnell, Kevin; Benezra, Robert; Brink, Robert; Swarbrick, Alexander; Mittal, Vivek.

In: Cancer Research, Vol. 70, No. 18, 15.09.2010, p. 7273-7282.

Research output: Contribution to journalArticle

Harvard

Mellick, AS, Plummer, PN, Nolan, DJ, Gao, D, Bambino, K, Hahn, M, Catena, R, Turner, V, McDonnell, K, Benezra, R, Brink, R, Swarbrick, A & Mittal, V 2010, 'Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth' Cancer Research, vol. 70, no. 18, pp. 7273-7282. https://doi.org/10.1158/0008-5472.CAN-10-1142

APA

Mellick, A. S., Plummer, P. N., Nolan, D. J., Gao, D., Bambino, K., Hahn, M., ... Mittal, V. (2010). Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth. Cancer Research, 70(18), 7273-7282. https://doi.org/10.1158/0008-5472.CAN-10-1142

Vancouver

Mellick AS, Plummer PN, Nolan DJ, Gao D, Bambino K, Hahn M et al. Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth. Cancer Research. 2010 Sep 15;70(18):7273-7282. https://doi.org/10.1158/0008-5472.CAN-10-1142

Author

Mellick, Albert S. ; Plummer, Prue N. ; Nolan, Daniel J. ; Gao, Dingcheng ; Bambino, Kathryn ; Hahn, Mary ; Catena, Raul ; Turner, Vivian ; McDonnell, Kevin ; Benezra, Robert ; Brink, Robert ; Swarbrick, Alexander ; Mittal, Vivek. / Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth. In: Cancer Research. 2010 ; Vol. 70, No. 18. pp. 7273-7282.

BibTeX

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title = "Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth",
abstract = "Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of a marker that can track EPCs from the BM to tumor neovasculature has impeded progress in understanding the molecular mechanisms underlying EPC biology. Here, we report the use of transgenic mouse and lentiviral models to monitor the BM-derived compartment of the tumor stroma; this approach exploits the selectivity of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced circulating EPCs and yielded significant defects in angiogenesis-mediated tumor growth. Additionally, use of the Id1 proximal promoter to express microRNA-30-based short hairpin RNA inhibited the expression of critical EPC-intrinsic factors, confirming that signaling through vascular endothelial growth factor receptor 2 is required for EPC-mediated tumor biology. By exploiting the selectivity of Id1 gene expression in EPCs, our results establish a strategy to track and target EPCs in vivo, clarifying the significant role that EPCs play in BM-mediated tumor angiogenesis.",
author = "Mellick, {Albert S.} and Plummer, {Prue N.} and Nolan, {Daniel J.} and Dingcheng Gao and Kathryn Bambino and Mary Hahn and Raul Catena and Vivian Turner and Kevin McDonnell and Robert Benezra and Robert Brink and Alexander Swarbrick and Vivek Mittal",
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language = "English",
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journal = "Cancer Research",
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publisher = "American Association for Cancer Research Inc.",
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RIS

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T1 - Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth

AU - Mellick, Albert S.

AU - Plummer, Prue N.

AU - Nolan, Daniel J.

AU - Gao, Dingcheng

AU - Bambino, Kathryn

AU - Hahn, Mary

AU - Catena, Raul

AU - Turner, Vivian

AU - McDonnell, Kevin

AU - Benezra, Robert

AU - Brink, Robert

AU - Swarbrick, Alexander

AU - Mittal, Vivek

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of a marker that can track EPCs from the BM to tumor neovasculature has impeded progress in understanding the molecular mechanisms underlying EPC biology. Here, we report the use of transgenic mouse and lentiviral models to monitor the BM-derived compartment of the tumor stroma; this approach exploits the selectivity of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced circulating EPCs and yielded significant defects in angiogenesis-mediated tumor growth. Additionally, use of the Id1 proximal promoter to express microRNA-30-based short hairpin RNA inhibited the expression of critical EPC-intrinsic factors, confirming that signaling through vascular endothelial growth factor receptor 2 is required for EPC-mediated tumor biology. By exploiting the selectivity of Id1 gene expression in EPCs, our results establish a strategy to track and target EPCs in vivo, clarifying the significant role that EPCs play in BM-mediated tumor angiogenesis.

AB - Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis-mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of a marker that can track EPCs from the BM to tumor neovasculature has impeded progress in understanding the molecular mechanisms underlying EPC biology. Here, we report the use of transgenic mouse and lentiviral models to monitor the BM-derived compartment of the tumor stroma; this approach exploits the selectivity of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced circulating EPCs and yielded significant defects in angiogenesis-mediated tumor growth. Additionally, use of the Id1 proximal promoter to express microRNA-30-based short hairpin RNA inhibited the expression of critical EPC-intrinsic factors, confirming that signaling through vascular endothelial growth factor receptor 2 is required for EPC-mediated tumor biology. By exploiting the selectivity of Id1 gene expression in EPCs, our results establish a strategy to track and target EPCs in vivo, clarifying the significant role that EPCs play in BM-mediated tumor angiogenesis.

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U2 - 10.1158/0008-5472.CAN-10-1142

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SP - 7273

EP - 7282

JO - Cancer Research

T2 - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 18

ER -

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