Proangiogenic factor PlGF programs CD11b+ myelomonocytes in breast cancer during differentiation of their hematopoietic progenitors
- Laurent, Julien Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Faes-van't Hull, Eveline Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Touvrey, Cedric Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Kuonen, François Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Lan, Qiang Department of Medicine, Faculty of Sciences, University of Fribourg, Switzerland
- Lorusso, Girieca Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
- Doucey, Marie-Agnès Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Ciarloni, Laura Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Imaizumi, Natsuko Division of Experimental Oncology, Universite de Lausanne, Switzerland
- Alghisi, Gian Carlo
- Fagiani, Ernesta University of Basel, Institute of Biochemistry and Genetics, Department of Biomedicine, Switzerland - Experimental Oncology, Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Zaman, Khalil Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Stupp, Roger Centre Pluridisciplinaire d'Oncologie, CHUV, Lausanne, Switzerland
- Shibuya, Masabumi Molecular Oncology, Tokyo Med. Dent. Univ., Japan
- Delaloye, Jean-François Obstetrics and Gynecology, CHUV, Lausanne, Switzerland
- Christofori, Gerhard Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Switzerland
- Rüegg, Curzio Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
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20.04.2011
Published in:
- Cancer Research. - 2011, vol. 71, no. 11, p. 3781-3791
English
Tumor-mobilized bone marrow-derived CD11b+ myeloid cells promote tumor angiogenesis, but how and when these cells acquire proangiogenic properties is not fully elucidated. Here we show that CD11b+ myelomonocytic cells develop proangiogenic properties during their differentiation from CD34+ hematopoietic progenitors and that Placenta Growth Factor (PlGF) is critical in promoting this education. Cultures of human CD34+ progenitors supplemented with conditioned medium from breast cancer cell lines or PlGF, but not from non-tumorigenic breast epithelial lines, generate CD11b+ cells capable of inducing endothelial cell sprouting in vitro and angiogenesis in vivo. An anti-Flt-1 mAb or soluble Flt-1 abolished the generation of proangiogenic activity during differentiation from progenitors cells. Moreover, inhibition of metalloproteinase activity, but not VEGF, during the endothelial sprouting assay blocked sprouting induced by these proangiogenic CD11b+ myelomonocytes. In a mouse model of breast cancer, circulating CD11b+ cells were proangiogenic in the sprouting assays. Silencing of PlGF in tumor cells prevented the generation of proangiogenic activity in circulating CD11b+ cells, inhibited tumor blood flow and slowed tumor growth. Peripheral blood of breast cancer patients at diagnosis, but not of healthy individuals, contained elevated levels of PlGF and circulating proangiogenic CD11b+ myelomonocytes. Taken together our results show that cancer cells can program proangiogenic activity in CD11b+ myelomonocytes during differentiation of their progenitor cells in a PlGF-dependent manner. These findings impact breast cancer biology, detection and treatment.
- Faculty
- Faculté des sciences et de médecine
- Department
- Médecine 3ème année
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 22816
- DOI 10.1158/0008-5472.CAN-10-3684
- Persistent URL
- https://folia.unifr.ch/unifr/documents/301893
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