Identification of genes expressed in tumor-associated macrophages
Identification of genes expressed in tumor-associated macrophages
复制标题
DOI：
10.1078/0171-2985-00246
复制
发表时间：
2003-01-01
期刊：
影响因子：
2.8
通讯作者：
Kreutz, M
中科院分区：
文献类型：
--
作者：
Gottfried, E;Faust, S;Kreutz, M
大多数恶性肿瘤含有所谓的肿瘤相关巨噬细胞（TAM）作为其白细胞浸润的主要成分。为了研究肿瘤微环境对巨噬细胞活化和分化的影响，我们通过在多细胞肿瘤球体内培养人单核细胞建立了三维模型系统。7天后，分离单核细胞衍生的TAM，并分析与无肿瘤细胞接触培养的巨噬细胞相比的表型改变。我们发现已知的巨噬细胞分化标志物羧肽酶M被抑制，而CD 14、HLA-DR和CD 16被上调。使用差异显示，我们确定了TAM和对照巨噬细胞之间差异表达的几个基因。氨脯氨酸二肽酶，一种已知影响中性粒细胞和巨噬细胞活性的化学吸引力的肽酶，在TAM中下调。相反，Toll样受体家族相关分子MD-1和RP 105通过肿瘤细胞接触在RNA和蛋白质水平上调，从我们的数据中，我们得出结论，TAM代表一个独特的巨噬细胞群体，其特征在于低表达分化相关的巨噬细胞抗原，但也由组成性激活状态。
Most malignant tumors contain so-called tumor-associated macrophages (TAM) as a major component of their leukocytic infiltrate. To investigate the impact of the tumor microenvironment on activation and differentiation of macrophages, we established a 3-dimensional model system by culturing human monocytes within multicellular tumor spheroids. After 7 days, monocyte-derived TAM were isolated and analyzed for phenotypic alterations as compared to macrophages cultured without tumor cell contact. We found the known macrophage differentiation marker Carboxypeptidase M to be suppressed while CD14, HLA-DR, and CD16 were up-regulated. Using Differential Display, we identified several genes that were differentially expressed between TAM and control macrophages. Prolidase, a peptidase known to influence the chemoattraction of neutrophils and macrophage activity, was down-regulated in TAM. In contrast, the Toll-like receptor family-related molecules MD-1 and RP105 were up-regulated by tumor cell contact, both at the RNA and protein level.From our data we conclude that TAM represent a distict macrophage population characterized by low expression of differentiation-associated macrophage antigens but also by a constitutive state of activation.