美国勒纳研究所Jeongwu Lee课题组发现，组织因子是放疗诱导胶质母细胞瘤重塑的关键调节因子。2023年7月13日，《癌细胞》杂志在线发表了这项成果。

研究人员表示，放射治疗（RT）为胶质母细胞瘤（GBM）患者提供了治疗益处，但不可避免地诱导了GBM及其微环境（TME）中鲜为人知的全局性变化，这些变化促进了放射抗性和复发。

通过细胞表面标志物筛选，研究人员发现CD142（组织因子或F3）在照射后衰老相关的β-半乳糖苷酶（SA-βGal）阳性GBM细胞中被强力诱导。F3促进辐照后SA-βGal⁺GBM细胞的克隆扩增，并通过激活肿瘤自主信号传导和外凝血通路协调致癌TME重塑。瘤内F3信号诱导间质样细胞状态转变和趋化因子分泌增加。同时，F3介导的病灶点高凝状态导致肿瘤相关巨噬细胞（TAM）的活化和细胞外基质（ECM）的重塑。一种新开发的F3靶向药物可有效抑制上述致癌事件并阻碍体内肿瘤复发。

这些研究结果支持F3是GBM治疗耐药和致癌衰老的关键调节因子，从而开辟了潜在的治疗途径。

附：英文原文

Title: Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling

Author: Hye-Min Jeon, Jeong-Yub Kim, Hee Jin Cho, Won Jun Lee, Dayna Nguyen, Sung Soo Kim, Young Taek Oh, Hee-Jin Kim, Chan-Woong Jung, Gonzalo Pinero, Tanvi Joshi, Dolores Hambardzumyan, Takuya Sakaguchi, Christopher G. Hubert, Thomas M. McIntyre, Howard A. Fine, Candece L. Gladson, Bingcheng Wang, Benjamin W. Purow, Jong Bae Park, Myung Jin Park, Do-Hyun Nam, Jeongwu Lee

Issue&Volume: 2023-07-13

Abstract: Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated β-galactosidase (SA-βGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-βGal+ GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues.

DOI: 10.1016/j.ccell.2023.06.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00217-9