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Phenotypic and functional characterization of proangiogenic monocytes
Author(s) -
Duda Dan G,
Jones Rosemary,
Dawson Michelle,
Capen Diane,
Tyrrell Alex,
Fukumura Dai,
Jain Rakesh K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.238.7
Subject(s) - progenitor cell , myeloid , population , angiogenesis , pathology , stromal cell , flow cytometry , intravital microscopy , bone marrow , microbiology and biotechnology , biology , mesenchymal stem cell , endothelial stem cell , cancer research , stem cell , immunology , in vivo , medicine , in vitro , biochemistry , environmental health
The function of proangiogenic monocytes in blood vessel assembly is currently unclear. We characterized myeloid progenitors among bone marrow‐derived cells (BMDCs) from 3 mouse strains by flow cytometry, and established their function in tumors by intravital and confocal microscopy. These cells expanded ex vivo , expressed PDGFRβ, c‐Kit and Sca1, and were distinct from mesenchymal and endothelial BMDCs. Implanted with tumor cells, they persisted and integrated into stroma but not tumor vessel walls, although they significantly promoted tumor growth and metastasis. We also studied myeloid progenitors in a model of capillary repair after hyperoxic acute lung injury. By immunogold labeling and flow cytometry, we detected a population of CD11b + CD45 + cells positive for VEGFR2 and PDGFRβ. We used high‐resolution imaging to capture sequential changes in these cells as they formed capillary walls. By transition to an endothelial or pericytic phenotype, these myeloid progenitor cells contributed to capillary repair, engrafting into the endothelial surface and aligning as perivascular cells. In summary, we show that a previously unrecognized population of myeloid cells can both promote tumor growth and function as common endothelial and perivascular cell precursors. Supported by R01‐ HL070866 , R01‐ CA115767 and AACR.