Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release
Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release
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DOI：
10.3892/ijo.2011.1055
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发表时间：
2011-08-01
影响因子：
5.2
通讯作者：
Mueller-Klieser, Wolfgang
中科院分区：
文献类型：
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作者：
Goetze, Kristina;Walenta, Stefan;Mueller-Klieser, Wolfgang
在实体恶性肿瘤中，乳酸已被认为是患者转移和总体生存的预后参数。为了研究乳酸对肿瘤细胞迁移的影响，采用Boyden小室实验。我们可以在这里表明，乳酸以剂量依赖的方式显著增强头颈癌细胞系的肿瘤细胞运动能力。肿瘤细胞迁移的改变可能归因于L-乳酸或乳酸转化为丙酮酸，因为只有这两种物质能够促进迁移。添加D-乳酸或改变渗透压或细胞内pH不会改变所研究细胞的迁移潜力。由于乳酸盐早些时候被证明在肿瘤球状模型中损害树突状细胞的穿透，这与本研究中恶性细胞群体的反应相反，因此我们将血液单核细胞作为一种高度能动性的免疫细胞类型和肿瘤相关巨噬细胞的前体纳入我们的检测。有趣的是，在pH值为7.4时，高浓度的L-乳酸(20 MM)抑制了单核细胞在博伊登小室系统中的迁移。此外，细胞因子TNF和IL-6的释放也受到抑制。这些数据表明，高乳酸含量通过促进肿瘤免疫逃逸现象和增强恶性细胞群体的迁移潜能来促进肿瘤进展，这可能直接导致更高的转移发生率。
In solid malignant tumors, lactate has been identified as a prognostic parameter for metastasis and overall survival of patients. To investigate the effects of lactate on tumor cell migration, Boyden chamber assays were applied. We could show here that lactate enhances tumor cell motility of head and neck carcinoma cell lines significantly in a dose-dependent manner. The changes in tumor cell migration could be attributed to L-lactate or a conversion of lactate to pyruvate, as only these two substances were able to increase migration. Addition of D-lactate or changes in osmolarity or intracellular pH did not alter the migratory potential of the cells investigated. Because lactate was shown earlier to impair the penetration of dendritic cells in a tumor spheroid model, which is contrary to the response of the malignant cell population in the present study, we included blood monocytes in our assay as a highly motile immune cell type and precursor of tumor-associated macrophages. interestingly, high levels of L-lactate (20 mM) at a pH of 7.4 inhibited monocyte migration in the Boyden chamber system. In addition, cytokine release of TNF and IL-6 was inhibited. The obtained data suggest that high lactate content promotes tumor progression by contributing to the phenomenon of tumor immune escape and by enhancing the migratory potential of the malignant cell population which may directly be coupled to a higher incidence of metastasis.