Conditioned media from macrophages of M1, but not M2 phenotype, inhibit the proliferation of the colon cancer cell lines HT-29 and CACO-2.

Conditioned media from macrophages of M1, but not M2 phenotype, inhibit the proliferation of the colon cancer cell lines HT-29 and CACO-2.
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DOI:
10.3892/ijo.2013.2203
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发表时间:
2014-02
影响因子:
5.2
通讯作者:
Wijkander J
Wijkander J
中科院分区:
医学2区
文献类型:
--
作者:
Engström A;Erlandsson A;Delbro D;Wijkander J

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实体瘤是由包括巨噬细胞在内的间质细胞渗透的,这些细胞可以影响肿瘤的生长、转移和血管生成。我们研究了来自不同巨噬细胞的条件培养液(CM)对结肠癌细胞株HT-29和CACO-2增殖的影响。来自THP-1巨噬细胞和单核细胞来源的人巨噬细胞的M1表型,而不是M2表型,以剂量依赖的方式抑制肿瘤细胞的增殖。用脂多糖和干扰素γ诱导巨噬细胞向M1表型分化,并在分化过程中(M1DIFF)和分化后(M1)产生CM。M1、M1DIFF CM和THP-1巨噬细胞CM可使HT-29细胞周期停滞,细胞周期中S期细胞减少,G2/M期增多。用M1DIFF处理HT-29细胞,但不处理M1或THP-1巨噬细胞CM,可导致约20%的肿瘤细胞凋亡,并伴随着在去除CM和随后在新鲜培养液中培养后细胞生长缺乏恢复。用蛋白质芯片鉴定M1和M2巨噬细胞释放的细胞因子。在M1巨噬细胞释放的细胞因子中,肿瘤坏死因子α和CXCL9通过直接加入HT-29细胞进行了检测,但都不影响细胞的增殖。我们的结果表明,M1巨噬细胞抑制了结肠癌细胞的生长,并具有在体内有助于减少肿瘤生长的潜力。
Solid tumors are infiltrated by stroma cells including macrophages and these cells can affect tumor growth, metastasis and angiogenesis. We have investigated the effects of conditioned media (CM) from different macrophages on the proliferation of the colon cancer cell lines HT-29 and CACO-2. CM from THP-1 macrophages and monocyte-derived human macrophages of the M1 phenotype, but not the M2 phenotype, inhibited proliferation of the tumor cells in a dose-dependent manner. Lipopolysaccaharide and interferon γ was used for differentiation of macrophages towards the M1 phenotype and CM were generated both during differentiation (M1DIFF) and after differentiation (M1). M1 and M1DIFF CM as well as THP-1 macrophage CM resulted in cell cycle arrest in HT-29 cells with a decrease of cells in S phase and an increase in G2/M phase. Treatment of HT-29 cells with M1DIFF, but not M1 or THP-1 macrophage CM, resulted in apoptosis of about 20% of the tumor cells and this was accompanied by lack of recovery of cell growth after removal of CM and subsequent culture in fresh media. A protein array was used to identify cytokines released from M1 and M2 macrophages. Among the cytokines released by M1 macrophages, tumor necrosis factor α and CXCL9 were tested by direct addition to HT-29 cells, but neither affected proliferation. Our results indicate that M1 macrophages inhibit colon cancer cell growth and have the potential of contributing to reducing tumor growth in vivo.
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