Journal ArticleDOI
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 +5 more
TLDR
It is shown 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.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.read more
Citations
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Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Journal ArticleDOI
Microenvironmental regulation of metastasis
TL;DR: Experimental data demonstrating the role of the microenvironment in metastasis is described, areas for future research are identified and possible new therapeutic avenues are suggested.
Journal ArticleDOI
EGFR Antagonists in Cancer Treatment
TL;DR: The mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer are discussed.
Journal ArticleDOI
VEGF-targeted therapy: mechanisms of anti-tumour activity
Lee M. Ellis,Daniel J. Hicklin +1 more
TL;DR: Several vascular endothelial growth factor (VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies.
Journal ArticleDOI
Tumor angiogenesis: molecular pathways and therapeutic targets
Sara M. Weis,David A. Cheresh +1 more
TL;DR: A durable and efficient antiangiogenic response will require approaches to simultaneously or sequentially target multiple aspects of the tumor microenvironment.
References
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Journal ArticleDOI
VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Rosandra N. Kaplan,Rebecca D. Riba,Stergios Zacharoulis,Anna H. Bramley,Loic Vincent,Carla Costa,Daniel D. MacDonald,David K. Jin,Koji Shido,Scott A. Kerns,Zhenping Zhu,Daniel J. Hicklin,Yan Wu,Jeffrey L. Port,Nasser K. Altorki,Elisa Port,Davide Ruggero,Sergey V. Shmelkov,Kristian K. Jensen,Shahin Rafii,David Lyden +20 more
TL;DR: A requirement for VEGFR1+ haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells is demonstrated.
Journal ArticleDOI
Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth
David Lyden,Koichi Hattori,Koichi Hattori,Sergio Dias,Carla Costa,Pamela Blaikie,Linda J. Butros,Amy Chadburn,Beate Heissig,Willy Marks,Larry Witte,Yan Wu,Daniel J. Hicklin,Zhenping Zhu,Neil R. Hackett,Ronald G. Crystal,Malcolm A.S. Moore,Katherine A. Hajjar,Katia Manova,Robert Benezra,Shahin Rafii +20 more
TL;DR: It is demonstrated that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggested new clinical strategies to block tumor growth are suggested.
Journal ArticleDOI
Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression.
TL;DR: Data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.
Journal ArticleDOI
Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis
TL;DR: The inflammatory chemoattractants S 100A8 and S100A9, whose expression is induced by distant primary tumours, attract Mac 1-myeloid cells in the premetastatic lung and may be common to both myeloid cell recruitment and tumour-cell invasion.
Journal ArticleDOI
Ectopic Expression of Oct-4 Blocks Progenitor-Cell Differentiation and Causes Dysplasia in Epithelial Tissues
TL;DR: Investigation of the effect of ectopic Oct-4 expression on somatic tissues of adult mice using a doxycycline-dependent expression system shows that certain adult progenitors remain competent to interpret key embryonic signals and support the notion that progenitor cells are a driving force in tumorigenesis.
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