文章：

CD44在胶质母细胞瘤侵袭、增殖及肿瘤复发中的作用：一项叙述性综述

A Narrative Review on CD44’s Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence

原文发布日期：9 October 2023

DOI: 10.3390/cancers15194898

类型: Article

开放获取: 是

英文摘要：

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5–2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5–5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence.

摘要翻译： 

胶质母细胞瘤（GBM）具有高度侵袭性的特征，这使得根治性切除几乎无法实现，从而导致肿瘤不可避免地复发。GBM复发可能是由于胶质瘤干细胞样细胞（GSCs）在多种治疗后存活所致。高表达CD44的GSCs具有高度侵袭性并对放化疗产生抵抗。CD44是一种多功能分子，通过多种信号通路促进肿瘤细胞的侵袭和增殖。其中，成对通路在不同缺氧条件下相互激活侵袭和增殖。严重缺氧（0.5–2.5% O2）上调缺氧诱导因子（HIF）-1α，进而激活包括CD44、TGF-β和cMET在内的靶基因，这些基因均与肿瘤迁移和侵袭相关。相反，中度缺氧（2.5–5% O2）上调HIF-2α，激活血管内皮生长因子（VEGF）/VEGFR2、cMYC和细胞周期蛋白D1等靶基因，这些基因均与肿瘤增殖相关。GBM周围的氧环境在肿瘤切除前后可能发生变化。切除前，肿瘤外周氧浓度处于严重缺氧状态；切除后的修复阶段，切除腔呈现中度缺氧。这些观察表明，严重缺氧下上调的CD44可能促进肿瘤细胞的迁移和侵袭。反之，当肿瘤切除导致中度缺氧时，上调的HIF-2α会激活其靶基因。由CD44调控的表型转换，根据缺氧条件在侵袭与增殖之间形成二分法，可能在GBM复发中起关键作用。

原文链接：

A Narrative Review on CD44’s Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence