迈阿密大学Anna Lasorella团队的一项最新研究提出空间同型聚类对癌细胞可塑性的抑制。相关论文于2025年9月18日发表在《癌细胞》杂志上。

该课题组定义了恶性细胞近端通讯在胶质母细胞瘤可塑性中的作用。该研究组发现，在与非恶性细胞有明确关系的同型细胞中，肿瘤细胞状态一致性最大，而随机分散的细胞则下调原始状态，获得不同的表型并在微环境中表现出变化。该课题组人员证明了胶质母细胞瘤细胞在原位母细胞瘤模型中发展成密集和分散的空间模式的内在倾向，并通过实验验证了细胞状态特异性的细胞粘附机制，该机制可以防止患者源性胶质母细胞瘤模型中药物干扰引起的表型偏差。研究团队在循环和单一乳腺癌细胞中建立了“同型细胞特性”的普遍性，并表明胶质母细胞瘤糖酵解-多代谢分散细胞状态独特地赋予较短的生存期，这为人类肿瘤中癌细胞的空间模式赋予了临床意义。

研究人员表示，肿瘤细胞可塑性引发的肿瘤异质性是治疗失败的关键。

附：英文原文

Title: Restraint of cancer cell plasticity by spatial homotypic clustering

Author: Simona Migliozzi, Bruno Adabbo, Luciano Garofano, Fan Wu, Pedro Davila, Ricardo J. Komotar, Michael E. Ivan, Ashish H. Shah, Benjamin B. Currall, Sion Williams, Daniel Bilbao Cortes, Melinda Minucci Boone, Macarena I. de la Fuente, Sakir H. Gultekin, Michele Ceccarelli, Antonio Iavarone, Anna Lasorella

Issue&Volume: 2025-09-18

Abstract: Tumor heterogeneity fueled by plasticity of cancer cells is a key to therapy failure. Here, we define the role of proximal communications of malignant cells in glioblastoma plasticity. We find that tumor cell state coherence is maximal in cells organized in homotypic clusters with defined relationships with non-malignant cells, whereas randomly dispersed cells downregulate the original state, acquire alternative phenotypes and exhibit changes in the microenvironment. We demonstrate the intrinsic propensity of glioblastoma cells to develop into clustered and dispersed spatial patterns in orthotopic mouse models and experimentally validate the cell state-specific mechanisms of cell-cell adhesion that prevent phenotype deviation with pharmacologic perturbations in patients-derived glioblastoma models. We establish the generality of “homotypic clustered cell identity” in circulating clustered and single breast cancer cells and show that the glioblastoma glycolytic-plurimetabolic dispersed cellular state uniquely confers shorter survival, thus assigning clinical significance to the spatial patterning of cancer cells in human tumors.

DOI: 10.1016/j.ccell.2025.08.009

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00366-6