Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis.
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.
Gao
Dingcheng
D
Cancer Genome Research Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Nolan
Daniel J
DJ
Mellick
Albert S
AS
Bambino
Kathryn
K
McDonnell
Kevin
K
Mittal
Vivek
V
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000473:pathology / Q000556:secondary*; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1