胶质瘤生存和细胞迁移对CD44表达水平的双相依赖性
Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level.
作者信息
Klank Rebecca L, Decker Grunke Stacy A, Bangasser Benjamin L, Forster Colleen L, Price Matthew A, Odde Thomas J, SantaCruz Karen S, Rosenfeld Steven S, Canoll Peter, Turley Eva A, McCarthy James B, Ohlfest John R, Odde David J
机构信息
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
Cell Rep. 2017 Jan 3;18(1):23-31. doi: 10.1016/j.celrep.2016.12.024.
While several studies link the cell-surface marker CD44 to cancer progression, conflicting results show both positive and negative correlations with increased CD44 levels. Here, we demonstrate that the survival outcomes of genetically induced glioma-bearing mice and of high-grade human glioma patients are biphasically correlated with CD44 level, with the poorest outcomes occurring at intermediate levels. Furthermore, the high-CD44-expressing mesenchymal subtype exhibited a positive trend of survival with increased CD44 level. Mouse cell migration rates in ex vivo brain slice cultures were also biphasically associated with CD44 level, with maximal migration corresponding to minimal survival. Cell simulations suggest that cell-substrate adhesiveness is sufficient to explain this biphasic migration. More generally, these results highlight the potential importance of non-monotonic relationships between survival and biomarkers associated with cancer progression.
虽然多项研究将细胞表面标志物CD44与癌症进展联系起来，但相互矛盾的结果表明，CD44水平升高与癌症进展呈正相关和负相关。在此，我们证明，基因诱导的荷胶质瘤小鼠和高级别人类胶质瘤患者的生存结果与CD44水平呈双相相关，最差的生存结果出现在中等水平。此外，高表达CD44的间充质亚型的生存率随CD44水平升高呈上升趋势。在体外脑片培养中，小鼠细胞迁移率也与CD44水平呈双相相关，最大迁移率对应最低生存率。细胞模拟表明，细胞与底物的粘附性足以解释这种双相迁移。更普遍地说，这些结果突出了生存与癌症进展相关生物标志物之间非单调关系的潜在重要性。
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