Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation
Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation
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LPS对小鼠髓系白血病细胞的双重作用：促增殖和抗增殖
DOI：
10.1016/j.yexcr.2016.03.006
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发表时间：
2016
影响因子：
3.7
通讯作者：
Yu Duonan
中科院分区：
文献类型：
--
作者：
Yu Lingling;Zhao Yingmin;Gu Xin;Wang Jijun;Pang Lei;Zhang Yanqing;Li Yaoyao;Jia Xiaoqin;Wang Xin;Gu Jian;Yu Duonan
改善骨髓微环境被认为是控制白血病细胞增殖、疾病进展和治疗后复发的一种有前途的策略。然而，由于白血病微环境中细胞和分子隔间的多样性和复杂性，很难剖析每一种单个分子或细胞类型在体内的作用。在这里，我们建立了一个体外系统来分析脂多糖(LPS)、基质细胞和内皮细胞在小鼠髓系肿瘤细胞和B淋巴瘤细胞生长中的作用。我们发现无论是以脂多糖还是骨髓基质细胞作为培养的饲养层，髓系肿瘤细胞的增殖都需要内毒素或骨髓基质细胞。令人惊讶的是，髓系白血病细胞在基质细胞上的生长在与内毒素联合培养时被强烈抑制。这种与内毒素相反的作用，即从促增殖到抗肿瘤生长的完全转变，至少部分是由于内毒素刺激的基质细胞迅速增加了IL-12、Fas配体和金属蛋白酶组织抑制因子-2的产生。这些结果表明，脂多糖可以促进或抑制肿瘤细胞的增殖，从而通过直接作用或调节肿瘤微环境来改变髓系白血病的病程。
Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment.