The scrambled story between hyaluronan and glioblastoma.
The scrambled story between hyaluronan and glioblastoma.
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DOI：
10.1016/j.jbc.2021.100549
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Lompardía SL
中科院分区：
文献类型：
--
作者：
Pibuel MA;Poodts D;Díaz M;Hajos SE;Lompardía SL
癌症生物学的进展揭示了癌细胞微环境对肿瘤发生和癌症进展的重要性。透明质酸（HA）是细胞外基质中的主要糖胺聚糖，几十年来一直与胶质母细胞瘤（GBM）的进展相关，胶质母细胞瘤是中枢神经系统中最常见和致命的原发性肿瘤。然而，HA 影响 GBM 特性和过程的机制一直难以阐明。在这篇综述中，我们对 HA 对 GBM 生物学影响的现有知识进行了全面评估，介绍了其主要受体 CD44 和 RHAMM 以及大量相关的下游信号通路，这些通路可以努力将 HA 活性与生物学结果直接联系起来。我们考虑了研究细胞外聚合物的复杂性以及用于尝试捕获其功能的不同策略，包括 2D 和 3D 体外研究、患者样本和体内模型。鉴于 HA 不仅影响迁移和侵袭，还影响细胞增殖、粘附和化疗耐药性，我们强调 HA 作为治疗靶点的潜在作用。最后，我们回顾了现有的不同方法来减少其促肿瘤效应，例如使用 4-甲基伞形酮、HA 寡聚物和透明质酸酶，并鼓励沿着这些方向进行进一步研究，以提高 GBM 患者的生存率和生活质量。
Advances in cancer biology are revealing the importance of the cancer cell microenvironment on tumorigenesis and cancer progression. Hyaluronan (HA), the main glycosaminoglycan in the extracellular matrix, has been associated with the progression of glioblastoma (GBM), the most frequent and lethal primary tumor in the central nervous system, for several decades. However, the mechanisms by which HA impacts GBM properties and processes have been difficult to elucidate. In this review, we provide a comprehensive assessment of the current knowledge on HA’s effects on GBM biology, introducing its primary receptors CD44 and RHAMM and the plethora of relevant downstream signaling pathways that can scramble efforts to directly link HA activity to biological outcomes. We consider the complexities of studying an extracellular polymer and the different strategies used to try to capture its function, including 2D and 3D in vitro studies, patient samples, and in vivo models. Given that HA affects not only migration and invasion, but also cell proliferation, adherence, and chemoresistance, we highlight the potential role of HA as a therapeutic target. Finally, we review the different existing approaches to diminish its protumor effects, such as the use of 4-methylumbelliferone, HA oligomers, and hyaluronidases and encourage further research along these lines in order to improve the survival and quality of life of GBM patients.
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