Albert Einstein Cancer Center

Gene expression analysis of macrophages that facilitate tumor invasion

Macrophages in the tumor microenvironment stimulate tumor cell migration, invasion, intravasation, and enhance angiogenesis. AECC investigators have shown that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor-CSF-1 paracrine loop. In this study, AECC investigators Pollard and Condeelis isolated invasion-promoting macrophages and compared their transcriptome to TAMs isolated indiscriminately. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, these observation suggest that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity. 

 
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