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 lethal macrometastasis is the major cause of death in cancer patients. Here, using mouse models of pulmonary metastasis, we identify bone marrow (BM)–derived endothelial progenitor cells (EPCs) as critical regulators of this angiogenic switch. We show that tumors induce expression of the transcription factor Id1 in the EPCs and that suppression of Id1 after metastatic colonization blocked EPC mobilization, caused angiogenesis inhibition, impaired pulmonary macrometastases, and increased survival of tumor-bearing animals. These findings establish the role of EPCs in metastatic progression in preclinical models and suggest that selective targeting of EPCs may merit investigation as a 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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Reply to Kerbel et al.: EPCs are again claimed to be essential in yet other models despite the irreproducibility of the original experiments introducing them.

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17{beta}-Estradiol Mobilizes Bone Marrow-Derived Endothelial Progenitor Cells to Tumors.

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Stem Cells and Cell Therapies in Lung Biology and Lung Diseases.

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Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth.

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