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

Abstract

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.

Keywords

• cancer-associated fibroblasts
• cancer-associated genes
• melanoma
• relative gene expression
• tumor-associated macrophages