Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis

By Dingcheng Gao, D. Nolan, A. Mellick, Kathryn Bambino, K. Mcdonnell, V. Mittal. Science, 2008

656 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ca10bb6cae1e09d81db18ac7750aa9198fac3d70

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Joyce
2. J. Talmadge
3. I. J. Fidler
4. J. Pollard
5. B. Psaila
6. B. Larrivée
7. C. Viallard
8. D. Lyden

In Oncology

1. J. Joyce
2. J. Pollard
3. J. Talmadge
4. I. J. Fidler
5. R. Weinberg
6. B. Psaila
7. B. Larrivée
8. C. Viallard

Citations in the corpus

• Tumor angiogenesis and vascular normalization: alternative therapeutic targets (2017, background): “MMTV-PyMT transgenic mice, which develop mammary tumors that metastasize to the lung, were used to demonstrate EPC contribution to the dynamics of vessel assembly that turns micrometastases into lethal macrometastases [71].”
• The metastatic niche: adapting the foreign soil (2009, background): “Recent studies exploring the cellular and molecular pathways that mediate the micrometastatic to macrometastatic switch identified bone marrow-derived endothelial progenitor cells (EPCs) as crucial regulators of this proces”
• AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective (2010, positive): “The blockade of EPCs by short hairpin RNA directed against the Id1 gene was found to inhibit angiogenesis at the micrometastatic stage and to impair subsequent growth (158).”
• Microenvironmental regulation of metastasis (2009, background): “These endothelial progenitor cells (EPCs) are recruited to macrometastases but not to micrometastases and are incorporated into the endothelial wal”
• Cancer to bone: a fatal attraction (2011, neutral): “Bone marrow-derived endothelial progenitors are under investigation as potential targets for anti-angiogenic strategie”