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.