Comparison of Invasive TAM sub-population to General TAM population. Mus musculus

The tumor microenvironment modifies the malignancy of tumors. In solid tumors this environment is populated by many macrophages (tumor-associated macrophages; TAMs) that in genetic studies that depleted these cells from mouse models of breast cancer were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these effects are through the stimulation of tumor cell migration, invasion, intravasation as well as an enhancement of angiogenesis. Using an in vivo invasion assay it was demonstrated that invasive carcinoma cells are a unique sub-population of tumor cells whose invasion and chemotaxis is dependent upon the co-migration of TAMs with obligate reciprocal signaling through an EGF/CSF-1 paracrine loop. In this study these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison to TAMs isolated indiscriminately to function using established macrophage markers by flow cytometry. Overall design: Five biological replicates for each population (Invasive and General TAM) were used.

肿瘤微环境（tumor microenvironment）可调控肿瘤的恶性进程。在实体瘤中，该微环境内富集大量肿瘤相关巨噬细胞（tumor-associated macrophages, TAMs）。既往遗传学研究证实，在乳腺癌小鼠模型中耗竭此类巨噬细胞，可促进肿瘤向恶性表型进展并提升其转移潜能。机制研究表明，此类巨噬细胞通过刺激肿瘤细胞的迁移、侵袭与内渗，同时增强血管生成，介导上述促瘤效应。利用体内侵袭实验证实，侵袭性癌细胞是一类独特的肿瘤细胞亚群，其侵袭与趋化过程依赖于与TAMs的共迁移，并通过表皮生长因子/集落刺激因子1（EGF/CSF-1）旁分泌环路实现双向信号交流。本研究分离了此类促侵袭性巨噬细胞，并通过流式细胞术利用已确立的巨噬细胞标志物，将其与未按功能分选的普通TAMs进行转录组学对比分析。实验总体设计：两类细胞群（侵袭性相关TAMs与普通TAMs）各设置5个生物学重复。