Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis

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.

Inhibition of β1 integrin and IL-3Rβ common subunit interaction hinders tumour angiogenesis

“…However, conflicting evidence has been reported in relation to their contribution to tumour vessel growth (Gao et al, 2008(Gao et al, , 2009, ranging from major (Lyden et al, 2001) to minor contribution (Peters et al, 2005) or no contribution at all (De Palma et al, 2005). Consistently, we were unable to show EPC incorporation into tumour nascent vessels when Kaposilike sarcoma cells were used as an in vivo model, although a small number of EPCs was detected in vessels formed by human-derived tumour endothelial cells.…”

Role of endothelial progenitor cells in breast cancer angiogenesis: from fundamental research to clinical ramifications

“…This idea is supported by a recent report by Gao et al [33] who found that although only 12% of the new blood vessels showed incorporation of EPC, blocking EPC mobilization caused severe angiogenesis inhibition and significantly impaired lung tumor progression. Moreover, in the same study, gene expression analysis of EPC revealed up-regulation of a variety of key proangiogenic genes including vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor receptor 1, chemokine ligands and receptors.…”

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

“…It has been shown that ID1 was essential for the metastasis of cancers to the lung in mouse models of cancer (13,18). Studies on cultured cells and mouse models have shown that levels of ID1 correlate with invasive as well as metastatic properties of cancer cells and that transfection of ID1 could make human breast cancer cells significantly more aggressive and metastatic (32).…”