Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study.

Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study.
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DOI:
10.3390/ijms19071880
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发表时间:
2018-06-26
影响因子:
5.6
通讯作者:
Woźniak M
Woźniak M
中科院分区:
生物学2区
文献类型:
--
作者:
Duś-Szachniewicz K;Drobczyński S;Ziółkowski P;Kołodziej P;Walaszek KM;Korzeniewska AK;Agrawal A;Kupczyk P;Woźniak M

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粘附对于维持细胞结构以及细胞间通讯至关重要,其功能障碍在癌症进展过程中普遍发生。近年来,越来越多的研究表明氧具有调节粘附分子表达的能力,然而,生理性缺氧(生理缺氧)对细胞粘附的影响仍然难以捉摸。因此,我们的目标是:(i)开发一种基于光镊的测定法,以精确评估常氧和生理氧下单个弥漫性大 B 细胞淋巴瘤(DLBCL)细胞与邻近细胞(间充质基质细胞)和细胞外基质(Matrigel)的粘附; (ii) 探讨整合素在单个淋巴瘤细胞粘附中的作用。我们发现,在生理氧作用下,淋巴瘤细胞系和原代淋巴细胞 B 对基质细胞和基质胶的粘附特性显着降低。在批量粘附测定中显示了相应的效果。然后我们强调,通过共聚焦显微镜研究,受损的 β1、β2 整合素和钙粘蛋白-2 表达是生理氧中淋巴细胞粘附减少的原因。此外,用抗整合素抗体进行的阻断研究揭示了整合素在淋巴瘤粘附中的关键作用。总而言之,所提出的方法可以精确确认生理性缺氧引起的单细胞粘附特性的变化。因此,我们的研究结果揭示了在体外研究肿瘤粘附时使用生理相关的氧调节和单细胞粘附方法的前所未有的作用。
Adhesion is critical for the maintenance of cellular structures as well as intercellular communication, and its dysfunction occurs prevalently during cancer progression. Recently, a growing number of studies indicated the ability of oxygen to regulate adhesion molecules expression, however, the influence of physiological hypoxia (physioxia) on cell adhesion remains elusive. Thus, here we aimed: (i) to develop an optical tweezers based assay to precisely evaluate single diffuse large B-cell lymphoma (DLBCL) cell adhesion to neighbor cells (mesenchymal stromal cells) and extracellular matrix (Matrigel) under normoxia and physioxia; and, (ii) to explore the role of integrins in adhesion of single lymphoma cell. We identified the pronouncedly reduced adhesive properties of lymphoma cell lines and primary lymphocytes B under physioxia to both stromal cells and Matrigel. Corresponding effects were shown in bulk adhesion assays. Then we emphasized that impaired β1, β2 integrins, and cadherin-2 expression, studied by confocal microscopy, account for reduction in lymphocyte adhesion in physioxia. Additionally, the blockade studies conducted with anti-integrin antibodies have revealed the critical role of integrins in lymphoma adhesion. To summarize, the presented approach allows for precise confirmation of the changes in single cell adhesion properties provoked by physiological hypoxia. Thus, our findings reveal an unprecedented role of using physiologically relevant oxygen conditioning and single cell adhesion approaches when investigating tumor adhesion in vitro.
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