Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
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*
Angiogenesis-mediated progression of micrometastasis to lethalmacrometastasis is the major cause of death in cancer patients.Here, using mouse models of pulmonary metastasis, we identifybone marrow (BM)–derived endothelial progenitor cells(EPCs) as critical regulators of this angiogenic switch. Weshow that tumors induce expression of the transcription factorId1 in the EPCs and that suppression of Id1 after metastaticcolonization blocked EPC mobilization, caused angiogenesis inhibition,impaired pulmonary macrometastases, and increased survival oftumor-bearing animals. These findings establish the role ofEPCs in metastatic progression in preclinical models and suggestthat selective targeting of EPCs may merit investigation asa 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
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Shahin Rafii and David Lyden (11 January 2008) Science319 (5860), 163.
[DOI: 10.1126/science.1153615] |Summary »|Full Text »|PDF »
In Science Signaling
EDITORS' CHOICE
Paula A. Kiberstis (15 January 2008) Sci. Signal.1 (2), ec21.
[DOI: 10.1126/stke.12ec21] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis.
R. C. Doebele, F. T. Schulze-Hoepfner, J. Hong, A. Chlenski, B. D. Zeitlin, K. Goel, S. Gomes, Y. Liu, M. K. Abe, J. E. Nor, et al. (2009)
Blood
114, 4592-4600
|Abstract »|Full Text »|PDF »
Suppression of Tumor Angiogenesis by G{alpha}13 Haploinsufficiency.
L. Chen, J. J. Zhang, S. Rafii, and X.-Y. Huang (2009)
J. Biol. Chem.
284, 27409-27415
|Abstract »|Full Text »|PDF »
Low-dose metronomic cyclophosphamide combined with vascular disrupting therapy induces potent antitumor activity in preclinical human tumor xenograft models.
L. G. Daenen, Y. Shaked, S. Man, P. Xu, E. E. Voest, R. M. Hoffman, D. J. Chaplin, and R. S. Kerbel (2009)
Mol. Cancer Ther.
8, 2872-2881
|Abstract »|Full Text »|PDF »
Glioma Tumor Stem-Like Cells Promote Tumor Angiogenesis and Vasculogenesis via Vascular Endothelial Growth Factor and Stromal-Derived Factor 1.
C. Folkins, Y. Shaked, S. Man, T. Tang, C. R. Lee, Z. Zhu, R. M. Hoffman, and R. S. Kerbel (2009)
Cancer Res.
69, 7243-7251
|Abstract »|Full Text »|PDF »
Blockade of Wnt Signaling Inhibits Angiogenesis and Tumor Growth in Hepatocellular Carcinoma.
J. Hu, A. Dong, V. Fernandez-Ruiz, J. Shan, M. Kawa, E. Martinez-Anso, J. Prieto, and C. Qian (2009)
Cancer Res.
69, 6951-6959
|Abstract »|Full Text »|PDF »
Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche.
H. C. Suh, M. Ji, J. Gooya, M. Lee, K. D. Klarmann, and J. R. Keller (2009)
Blood
114, 1186-1195
|Abstract »|Full Text »|PDF »
Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1.
S.-Y. Kang, O. J. Halvorsen, K. Gravdal, N. Bhattacharya, J. M. Lee, N. W. Liu, B. T. Johnston, A. B. Johnston, S. A. Haukaas, K. Aamodt, et al. (2009)
PNAS
106, 12115-12120
|Abstract »|Full Text »|PDF »
High Levels of Circulating VEGFR2+ Bone Marrow-Derived Progenitor Cells Correlate with Metastatic Disease in Patients with Pediatric Solid Malignancies.
M. Taylor, J. Rossler, B. Geoerger, A. Laplanche, O. Hartmann, G. Vassal, and F. Farace (2009)
Clin. Cancer Res.
15, 4561-4571
|Abstract »|Full Text »|PDF »
Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.
A. Reinisch, N. A. Hofmann, A. C. Obenauf, K. Kashofer, E. Rohde, K. Schallmoser, K. Flicker, G. Lanzer, W. Linkesch, M. R. Speicher, et al. (2009)
Blood
113, 6716-6725
|Abstract »|Full Text »|PDF »
Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice.
White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models.
Y. Zhang, A. Daquinag, D. O. Traktuev, F. Amaya-Manzanares, P. J. Simmons, K. L. March, R. Pasqualini, W. Arap, and M. G. Kolonin (2009)
Cancer Res.
69, 5259-5266
|Abstract »|Full Text »|PDF »
Stem Cells and the Natural History of Lung Cancer: Implications for Lung Cancer Screening.
R. J. van Klaveren, S. C. van't Westeinde, B.-J. de Hoop, and H. C. Hoogsteden (2009)
Clin. Cancer Res.
15, 2215-2218
|Abstract »|Full Text »|PDF »
Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis.
H. Chen, R. A. Campbell, Y. Chang, M. Li, C. S. Wang, J. Li, E. Sanchez, M. Share, J. Steinberg, A. Berenson, et al. (2009)
Blood
113, 1992-2002
|Abstract »|Full Text »|PDF »
Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLC{beta}2 axis.
Y.-S. Maeng, H.-J. Choi, J.-Y. Kwon, Y.-W. Park, K.-S. Choi, J.-K. Min, Y.-H. Kim, P.-G. Suh, K.-S. Kang, M.-H. Won, et al. (2009)
Blood
113, 233-243
|Abstract »|Full Text »|PDF »
TSU68 Prevents Liver Metastasis of Colon Cancer Xenografts by Modulating the Premetastatic Niche.
M. Yamamoto, H. Kikuchi, M. Ohta, T. Kawabata, Y. Hiramatsu, K. Kondo, M. Baba, K. Kamiya, T. Tanaka, M. Kitagawa, et al. (2008)
Cancer Res.
68, 9754-9762
|Abstract »|Full Text »|PDF »
Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression.
M. Aleku, P. Schulz, O. Keil, A. Santel, U. Schaeper, B. Dieckhoff, O. Janke, J. Endruschat, B. Durieux, N. Roder, et al. (2008)
Cancer Res.
68, 9788-9798
|Abstract »|Full Text »|PDF »
Combination of antiangiogenesis with chemotherapy for more effective cancer treatment.
Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas.
R. S. Kerbel, R. Benezra, D. C. Lyden, K. Hattori, B. Heissig, D. J. Nolan, V. Mittal, Y. Shaked, S. Dias, F. Bertolini, et al. (2008)
PNAS
105, E54
|Full Text »|PDF »
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.
P. Salven, S. Purhonen, D. Rossi, S. Yla-Herttuala, K. Alitalo, and I. L. Weissman (2008)
PNAS
105, E55
|Full Text »|PDF »
17{beta}-Estradiol Mobilizes Bone Marrow-Derived Endothelial Progenitor Cells to Tumors.
R. Suriano, D. Chaudhuri, R. S. Johnson, E. Lambers, B. T. Ashok, R. Kishore, and R. K. Tiwari (2008)
Cancer Res.
68, 6038-6042
|Abstract »|Full Text »|PDF »
Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.
R. G. Bagley, C. Rouleau, T. St. Martin, P. Boutin, W. Weber, M. Ruzek, N. Honma, M. Nacht, S. Shankara, S. Kataoka, et al. (2008)
Mol. Cancer Ther.
7, 2536-2546
|Abstract »|Full Text »|PDF »
Stem Cells and Cell Therapies in Lung Biology and Lung Diseases.
D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop (2008)
Proceedings of the ATS
5, 637-667
|Full Text »|PDF »
Review: Endothelial progenitor cells: markers of vascular reparative capacity.
T. J. Povsic and P. J. Goldschmidt-Clermont (2008)
Therapeutic Advances in Cardiovascular Disease
2, 199-213
|Abstract »|PDF »
Tumor Angiogenesis.
R. S. Kerbel (2008)
N. Engl. J. Med.
358, 2039-2049
|Full Text »|PDF »
Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth.
S. Purhonen, J. Palm, D. Rossi, N. Kaskenpaa, I. Rajantie, S. Yla-Herttuala, K. Alitalo, I. L. Weissman, and P. Salven (2008)
PNAS
105, 6620-6625
|Abstract »|Full Text »|PDF »
Migratory neighbors and distant invaders: tumor-associated niche cells.
J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden (2008)
Genes & Dev.
22, 559-574
|Abstract »|Full Text »|PDF »