Li Guilong, Cai Jiaying, Xie Jianjun, Dai Yizhi
Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, The People's Republic of China.
Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, The People's Republic of China.
Open Life Sci. 2023 Sep 19;18(1):20220716. doi: 10.1515/biol-2022-0716. eCollection 2023.
The extracellular matrix (ECM) has been strongly correlated with cancer progression in various tumor types. However, the specific mechanisms underlying ECM-associated tumor behaviors remain unclear. In this study, we found an enriched distribution of fibrin in tumor tissues obtained from high-grade non-small cell lung cancer (NSCLC) patients. For further investigation, we established an 3D culture system using fibrin gel and found that NSCLC cells grown in this system exhibited increased stemness and tumorigenesis. Mechanistically, we demonstrated that fibrin facilitated the activation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway through integrin β1. Furthermore, we found that blocking integrin β1 signals enhanced the tumor suppressive effects of chemotherapy, providing a novel approach for clinical therapy for NSCLC.
细胞外基质（ECM）与多种肿瘤类型的癌症进展密切相关。然而，ECM相关肿瘤行为的具体机制仍不清楚。在本研究中，我们发现从高级别非小细胞肺癌（NSCLC）患者获得的肿瘤组织中纤维蛋白分布丰富。为了进一步研究，我们使用纤维蛋白凝胶建立了一个三维培养系统，发现生长在该系统中的NSCLC细胞表现出更高的干性和肿瘤发生能力。从机制上讲，我们证明纤维蛋白通过整合素β1促进了磷酸酶和张力蛋白同源物（PTEN）/蛋白激酶B（AKT）信号通路的激活。此外，我们发现阻断整合素β1信号增强了化疗的肿瘤抑制作用，为NSCLC的临床治疗提供了一种新方法。
