The prognostic effect of mechanical, ultrastructural, and ECM signatures in glioblastoma core and rim.

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL
APL Bioengineering Pub Date : 2024-06-24 eCollection Date: 2024-09-01 DOI:10.1063/5.0203570
Bradley J Mahaffey, Zachary P Fowler, Zoe Lung, Vivien Dang, Hyunchul Lee, Allison McKenzie Johnson, Marco A Munoz, Dylan A Goodin, Hermann B Frieboes, Brian J Williams, Joseph Chen
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Abstract

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

胶质母细胞瘤核心和边缘的机械、超微结构和 ECM 特征对预后的影响。
胶质母细胞瘤(GBM)是一种高度侵袭性、侵袭性脑癌,中位生存期仅为 15 个月,对标准疗法具有抗药性。最近的研究表明,瘤内异质性通过微环境线索介导肿瘤适应,在促进耐药性方面发挥着关键作用。GBM 可分为两个不同的区域--核心区和边缘区,这两个区域被认为驱动着肿瘤演变的特定方面。这些区域的生物分子和生物物理信号调控着肿瘤进展的这些差异,但对其细胞生物物理特征的描述仍然很少。本研究调查了患者匹配的 GBM 核心和边缘组织中肿瘤细胞外基质(ECM)的机械和超微结构特征。研究人员使用原子力显微镜、扫描电子显微镜和免疫荧光成像技术分析了 7 个患者匹配的肿瘤核心和边缘样本以及 1 个非肿瘤性对照,以量化机械、超微结构和 ECM 成分的变化。结果显示,GBM 核心、边缘和非肿瘤组织之间的生物物理参数存在明显差异。与肿瘤边缘和非肿瘤组织相比,GBM 核心更硬、更致密,富含 ECM 蛋白透明质酸和 tenascin-C。这些改变密切相关,对预后有影响,僵硬、致密的组织与较长的无进展生存期相关。这些发现揭示了 GBM 肿瘤微环境中生物物理参数空间异质性的新见解,并确定了一组可能与患者预后相关的特征。从长远来看,这些特征可能有助于开发对抗治疗耐药性的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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