Gene Expression Analysis of Macrophages That Facilitate Tumor Invasion Supports a Role for Wnt-Signaling in Mediating Their Activity in Primary Mammary Tumors

摘要: The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models breast cancer, were shown to promote progression and increase metastatic potential. Mechanistic showed tumor-promoting effects are through stimulation cell migration, invasion, intravasation, enhancement angiogenesis. Using an vivo invasion assay, it was demonstrated invasive carcinoma a unique subpopulation whose chemotaxis dependent on comigration tumor-associated (TAMs) with obligate reciprocal signaling epidermal growth factor-CSF-1 paracrine loop. study, invasion-promoting isolated subjected analysis their transcriptome comparison TAMs indiscriminately function using established macrophage markers. Unsupervised transcript patterns invasion-associated represent gene ontology criteria, have expression related tissue organ development. Gene set enrichment also specifically enriched for molecules involved Wnt-signaling. Previously, macrophage-derived Wnt vascular remodeling highly motile intravasate around perivascular TAM clusters. Taken together, we conjecture link angiogenesis Wnt-signaling plays role mediating activity.