Proangiogenic Factor PlGF Programs CD11b+ Myelomonocytes in Breast Cancer during Differentiation of Their Hematopoietic Progenitors
| Autor: | Masabumi Shibuya, Khalil Zaman, Qiang Lan, Curzio Rüegg, François Kuonen, Girieca Lorusso, Roger Stupp, Natsuko Imaizumi, Ernesta Fagiani, Julien Laurent, Marie Agnès Doucey, Jean François Delaloye, Gerhard Christofori, Gian Carlo Alghisi, Cédric Touvrey, Laura Ciarloni, Eveline Faes-van't Hull |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Angiogenesis Cellular differentiation CD34 Expression Antigens CD34 Pregnancy Proteins Pgf Isoforms Monocytes Metastasis Mice 0302 clinical medicine Pregnancy Medicine Mice Inbred BALB C 0303 health sciences CD11b Antigen Cell Differentiation Middle Aged Fetal Blood Recombinant Proteins 3. Good health Endothelial stem cell Haematopoiesis Oncology Tumor Angiogenesis 030220 oncology & carcinogenesis Female Recruitment Stem cell Adult medicine.medical_specialty Cells Breast Neoplasms Factor Receptor-1 03 medical and health sciences Cell Line Tumor Internal medicine Animals Humans Placenta Growth-Factor Progenitor cell Neovascularization Aged Placenta Growth Factor 030304 developmental biology business.industry Hematopoietic Stem Cells Endocrinology Cancer cell Cancer research Prognostic-Significance business |
| Zdroj: | Cancer research |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-10-3684 |
| Popis: | 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 nontumorigenic 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 progenitor 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. Cancer Res; 71(11); 3781–91. ©2011 AACR. |
| Databáze: | OpenAIRE |
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