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Pattern of expression of immune- and stroma-associated genes in blood of mice with experimental B16 melanoma

机译:实验B16黑色素瘤小鼠血液中免疫和基质相关基因的表达模式

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The interaction between malignant and stromal cells represents a major cross-talk pathway upon carcinogenesis. Cellular elements of the reactive tumor stroma are a heterogeneous population which are represented specifically by cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAM). It is not known whether expression of CAF- and TAM-associated genes could be detected in the peripheral blood of cancer patients to monitor a course of disease. The aim of the study was to assess the relative expression (RE) of cancer-related genes in peripheral blood of mice with experimental melanoma. Quantitative PCR was used to determine RE of 15 genes in the blood of C57BL/6j control mice and mice with injected B16 melanoma cells. The Kruskal-Wallis and the Fischer exact tests with correction on multiple comparisons, according to the Benjamini-Hochberg procedure with FDR = 0.2 were used for statistical analysis. Analysis of 15 immune and stromal markers RE showed differentiated expression of several CAF and TAM markers in mice with experimental melanoma in comparison with the control animals. Thus, CAF markers Acta2 , Cxcl14 , Fap and TAM markers Cd68 , Ccl22 and Ccl17 were significantly upregulated, while Cd4 , Cd3 were downregulated. This, together with increased expression of Cox-2 suggested a stable immunosuppressive state of mice with experimental melanomas. The results of the study showed that potential markers of cancer-associated fibroblasts and tumor-associated macrophages in peripheral blood of mice with experimental melanoma could be used for non-invasive detection of melanoma cell progression.
机译:恶性和基质细胞之间的相互作用代表了致癌物中的主要串扰途径。反应性肿瘤基质的细胞元素是异质群,其特异性地由癌症相关的成纤维细胞(CAF)和肿瘤相关的巨噬细胞(TAM)表示。不知道是否可以在癌症患者的外周血中检测到CAF-和TAM-相关基因的表达,以监测疾病病程。该研究的目的是评估用实验黑素瘤的小鼠外周血中癌症相关基因的相对表达(RE)。使用定量PCR以在C57BL / 6J对照小鼠和小鼠的血液中测定15个基因的RE,注射B16黑色素瘤细胞。根据Benjamini-Hochberg程序,Kruskal-Wallis和Fischer对多种比较进行校正,根据FDR = 0.2进行统计分析。与对照动物相比,对15种免疫和基质标记物的分析显示,实验黑色素瘤的小鼠中的几个CAF和TAM标记的分化表达。因此,CAF标记物acta2,CXCl14,FAP和TAM标志物CD68,CCL22和CCL17显着上调,而CD4,CD3被下调。这与COX-2的表达的增加表明,具有实验黑色素瘤的稳定免疫抑制状态。该研究的结果表明,具有实验黑素瘤的小鼠外周血中的癌症相关成纤维细胞和肿瘤相关巨噬细胞的潜在标志物可用于黑色素瘤细胞进展的非侵入性检测。

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