Sawa-Wejksza Katarzyna, Dudek Adrianna, Lemieszek Marta, Kaławaj Katarzyna, Kandefer-Szerszeń Martyna
1 Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
2 Department of Medical Biology, Institute of Rural Health, Lublin, Poland.
Tumour Biol. 2018 Sep;40(9):1010428318797880. doi: 10.1177/1010428318797880.
Macrophages play an important role in the immune response and in the maintenance of tissue homeostasis. It is well known that many tumors recruit monocytes from circulation and influence their differentiation, mainly into suppressive M2-like subsets. Since there are contradictory data concerning the importance of macrophages for colon cancer progression, we used in our experiments four colon cancer cell lines representing different stages of tumor development (HT29, LS180, SW948, SW620). An acute monocytic leukemia cell line THP-1 was used as a human model of monocytes. Our work revealed that conditioned medium from the tumor cell lines induced activation and differentiation of THP-1 cells. The changes involved increased expression of CD68, a macrophage differentiation marker. Moreover, we also observed increased expression of CD206 and CD163, which are widely considered as markers of tumor-associated macrophages. The tumor-derived conditioned medium decreased the proliferation of THP-1 cells and blocked their cell cycle at the G1 stage. The tumor-conditioned medium also upregulated the production of several cytokines and chemokines characteristic of both M1 and M2 subsets and induced the expression of important pro-angiogenic factors, vascular endothelial growth factor, and matrix metalloproteinase-9 in THP-1 cells. Moreover, the tumor-conditioned medium induced the expression of galectin-3, which is implicated in malignant transformation, and indoleamine 2,3-dioxygenase, that is, a key enzyme of the kynurenine pathway. Our data suggest that tumor cells can actively influence the phenotype of monocytes and switch their differentiation into a population of non-adherent mixed M1 and M2 cells. These preliminary studies suggest that colon cancer cells produce soluble factors that influence monocyte differentiation, most probably into suppressive subsets. These data provide a better understanding of the influence of colon cancer on polarization of monocytes.
巨噬细胞在免疫反应和组织稳态维持中发挥着重要作用。众所周知，许多肿瘤会从循环中招募单核细胞并影响其分化，主要分化为抑制性的M2样亚群。由于关于巨噬细胞对结肠癌进展的重要性存在相互矛盾的数据，我们在实验中使用了代表肿瘤发展不同阶段的四种结肠癌细胞系（HT29、LS180、SW948、SW620）。急性单核细胞白血病细胞系THP-1被用作单核细胞的人类模型。我们的研究表明，肿瘤细胞系的条件培养基可诱导THP-1细胞的激活和分化。这些变化包括巨噬细胞分化标志物CD68表达增加。此外，我们还观察到CD206和CD163的表达增加，它们被广泛认为是肿瘤相关巨噬细胞的标志物。肿瘤来源的条件培养基降低了THP-1细胞的增殖，并在G1期阻断其细胞周期。肿瘤条件培养基还上调了M1和M2亚群特有的几种细胞因子和趋化因子的产生，并诱导THP-1细胞中重要的促血管生成因子、血管内皮生长因子和基质金属蛋白酶-9的表达。此外，肿瘤条件培养基诱导了参与恶性转化的半乳糖凝集素-3和色氨酸途径的关键酶吲哚胺2,3-双加氧酶的表达。我们的数据表明，肿瘤细胞可以积极影响单核细胞的表型，并将其分化转变为非贴壁的混合M1和M2细胞群体。这些初步研究表明，结肠癌细胞产生影响单核细胞分化的可溶性因子，很可能是分化为抑制性亚群。这些数据有助于更好地理解结肠癌对单核细胞极化的影响。
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