title: Unique expression patterns associated with preferential recruitment of immature myeloid cells into angiogenic versus dormant tumors.
abstract: Cancer progression from microscopic dormant tumors into disseminated disease involves tumor angiogenesis, and is commonly referred to as the 'angiogenic switch'. CD11b(+)Gr1(+) immature myeloid cells (IMCs) were reported to promote angiogenesis and tumor progression. Here, we studied a model of tumor dormancy, in which Lewis Lung Carcinoma tumor cells were inoculated intra-abdominally into C57Bl/6J mice. Dormancy versus expansive growth was determined by the site of tumor implantation (lower vs upper abdomen). Global gene expression of IMCs was evaluated in different stages of recruitment, starting in the bone marrow, followed by the peripheral blood and finally in the vascular versus dormant tumors. We first demonstrated a ∼3 fold enrichment of IMCs within vascular tumors as compared with dormant tumors, correlating with tumor-infiltrating CD31(+) endothelial cells. Although their migration from the PB into dormant tumors led to differential expression of a relatively small number of genes, recruitment of IMCs into the upper tumors was associated with a profound transcriptional response. Importantly, a large set of proangiogenic genes were significantly upregulated in IMCs derived from vascular tumors compared with those derived from dormant tumors. We therefore, suggest that proangiogenic versus nonangiogenic transcriptional patterns is associated with the ability of IMCs to promote tumor angiogenesis.
authors.affiliation: Laboratory for Reproductive Immunology, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Pencovich
authors.forename: S
authors.initials: S
authors.lastname: Hantisteanu
authors.forename: O
authors.initials: O
authors.lastname: Wurtzel
authors.forename: M
authors.initials: M
authors.lastname: Hallak
authors.forename: O
authors.initials: O
authors.lastname: Fainaru
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018827:Carcinoma, Lewis Lung; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018797:Cell Cycle Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A