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Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis
Dingcheng Gao,
Daniel J. Nolan,
Albert S. Mellick,
Kathryn Bambino,
Kevin McDonnell,
Vivek Mittal*
Abstract:
Angiogenesis-mediated progression of micrometastasis to lethalmacrometastasis is the major cause of death in cancer patients.Here, using mouse models of pulmonary metastasis, we identifybone marrow (BM)–derived endothelial progenitor cells(EPCs) as critical regulators of this angiogenic switch. Weshow that tumors induce expression of the transcription factorId1 in the EPCs and that suppression of Id1 after metastaticcolonization blocked EPC mobilization, caused angiogenesis inhibition,impaired pulmonary macrometastases, and increased survival oftumor-bearing animals. These findings establish the role ofEPCs in metastatic progression in preclinical models and suggestthat selective targeting of EPCs may merit investigation asa therapy for cancer patients with lung metastases.
Cancer Genome Research Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
* To whom correspondence should be addressed. E-mail: mittal{at}cshl.edu
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