Farsinejad Sadaf, Centeno Daniel, Savas-Carstens Jan, Polotaye Teagan, Pavlovič Tonja, Babvey Pouria, Muranen Taru, Miedziarek Cezary, Jasiński Piotr, Dziabaszewska Elżbieta, Zaborowski Mikołaj Piotr, Lum Pek Yee, Martin Laura A, Iwanicki Marcin P
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
Cancers (Basel). 2025 Apr 27;17(9):1472. doi: 10.3390/cancers17091472.
: The role of extracellular matrix adhesion components in modulation of the treatment sensitivity of ovarian cancer (OC) cells is not well understood. : Analysis of ovarian cancer TCGA gene expression datasets revealed an inverse correlation between genes involved in cell-cycle progression and extracellular matrix interactions, including laminin-binding receptor integrin β4, a major component of extracellular matrix adhesion. Gene ontology analysis also showed that in patient populations with low expression, cell cycle-related programs were activated, while in populations with high expression of , the activation of these cell cycle programs was lower. Suppression of proliferation with the CDK4/6 inhibitor Palbociclib stimulated integrin β4 expression and induced protection against Cisplatin in cells naturally expressing low levels of integrin β4. Additionally, ovarian cancer patient-derived organoids showed reduced Cisplatin sensitivity when pretreated with Palbociclib. Our data also showed that integrin β4 overexpression decreased ovarian cancer cell proliferation and at the same time, attenuated Cisplatin response. : In summary, our investigations support the idea that integrin β4, and likely its matrix ligands, play critical roles in the regulation of cellular growth and the chemoresistance of ovarian cancer cells.
细胞外基质黏附成分在调节卵巢癌细胞（OC）治疗敏感性中的作用尚未完全明确。对卵巢癌TCGA基因表达数据集的分析显示，参与细胞周期进程的基因与细胞外基质相互作用相关基因之间存在负相关，其中包括层粘连蛋白结合受体整合素β4，它是细胞外基质黏附的主要成分。基因本体分析还表明，在低表达的患者群体中，细胞周期相关程序被激活，而在高表达群体中，这些细胞周期程序的激活程度较低。用CDK4/6抑制剂帕博西尼抑制增殖可刺激整合素β4表达，并在天然表达低水平整合素β4的细胞中诱导对顺铂的保护作用。此外，卵巢癌患者来源的类器官在用帕博西尼预处理后对顺铂的敏感性降低。我们的数据还表明，整合素β4过表达可降低卵巢癌细胞增殖，同时减弱对顺铂的反应。总之，我们的研究支持这样一种观点，即整合素β4及其可能的基质配体在调节细胞生长和卵巢癌细胞的化疗耐药性中起关键作用。
