Mechanical activation and expression of HSP27 in epithelial ovarian cancer.
Mechanical activation and expression of HSP27 in epithelial ovarian cancer.
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上皮性卵巢癌中热休克蛋白27（HSP27）的机械激活与表达
DOI：
10.1038/s41598-024-52992-7
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发表时间：
2024-02-03
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
了解复杂的生物力学肿瘤微环境(TME)对于开发下一代抗癌治疗策略至关重要。尤其是上皮性卵巢癌(EOC)，这是由于复发或化疗耐药导致的最致命的妇科癌症。然而，目前的EOC进展模型几乎不能控制或监测生物力学参数的变化如何改变EOC细胞的行为。在这项研究中，我们提出了一种微流控装置，旨在允许对卵巢TME进行生物力学研究。利用这个显微组织系统，我们描述了以拉伸应变形式的生物机械刺激如何上调HSP27的磷酸化，HSP27是一种与卵巢癌化疗耐药有关的热休克蛋白。此外，在体外血管化的TME模型中，经菌株处理的EOC细胞对紫杉醇的反应降低。这一结果与生物力学调节HSP27作为EOC化疗耐药的媒介有直接联系，这可能解释了一些患者这种治疗失败的原因。这项工作为阐明包括化疗耐药在内的EOC进展的机制生物学调控奠定了基础，并可能为抗癌治疗提供新的靶点。
Understanding the complex biomechanical tumor microenvironment (TME) is of critical importance in developing the next generation of anti-cancer treatment strategies. This is especially true in epithelial ovarian cancer (EOC), the deadliest of the gynecologic cancers due to recurrent disease or chemoresistance. However, current models of EOC progression provide little control or ability to monitor how changes in biomechanical parameters alter EOC cell behaviors. In this study, we present a microfluidic device designed to permit biomechanical investigations of the ovarian TME. Using this microtissue system, we describe how biomechanical stimulation in the form of tensile strains upregulate phosphorylation of HSP27, a heat shock protein implicated in ovarian cancer chemoresistance. Furthermore, EOC cells treated with strain demonstrate decreased response to paclitaxel in the in vitro vascularized TME model. The results provide a direct link to biomechanical regulation of HSP27 as a mediator of EOC chemoresistance, possibly explaining the failure of such therapies in some patients. The work presented here lays a foundation to elucidating mechanobiological regulation of EOC progression, including chemoresistance and could provide novel targets for anti-cancer therapeutics.
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影响因子：
4.6
作者：
Ip CK;Li SS;Tang MY;Sy SK;Ren Y;Shum HC;Wong AS
通讯作者：
Wong AS
影响因子：
2.9
作者：
Hendricks, Peter;Diaz, Francisco J.;Nirmalanandhan, Victor Sanjit
通讯作者：
Nirmalanandhan, Victor Sanjit
影响因子：
3.7
作者：
Katsogiannou M;Andrieu C;Rocchi P
通讯作者：
Rocchi P
影响因子：
4
作者：
Carduner, L.;Leroy-Dudal, J.;Kellouche, S.
通讯作者：
Kellouche, S.
影响因子：
4.2
作者：
Chen, Ya-Shan;Huang, Tse-Hung;Shen, Chia-Rui
通讯作者：
Shen, Chia-Rui