Abstract
Background: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. Methods: An in vitro study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. Results: In the in vitro study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. Conclusion: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.
Highlights
Tumour-associated macrophages (TAMs) are unique tumour-infiltrating leukocytes that directly affect tumour progression, according to the anti (M1) or pro (M2) tumour phenotype
The expression levels of CD11b in myeloid cells (Figure 2B), lymphocyte antigen 6 complex, locus C (Ly6C) in monocytes and M1 tumour-associated macrophages (TAMs) (Figure 2C), and F4/80 in macrophages (Figure 2D) were increased significantly in the bone marrow (BM) and CT26 co-cultured cells in the presence of POM-1 compared with the absence of POM-1 (CD11b, 45.15 ± 1.95% vs. 41.96 ± 1.38%, p < 0.05; Ly6C, 1.20 ± 0.21% vs. 0.78 ± 0.15%, p < 0.05; F4/80, 0.59 ± 0.12% vs. 0.20 ± 0.07%, p < 0.001)
Major histocompatibility complex (MHC) class II expression did not differ in the BM and CT26 co-cultures according to POM-1 treatment (Figure 2E)
Summary
Tumour-associated macrophages (TAMs) are unique tumour-infiltrating leukocytes that directly affect tumour progression, according to the anti (M1) or pro (M2) tumour phenotype. This study was designed to investigate the effect of cluster differentiation (CD) and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. Conclusion: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue
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