Verhagen Mathijs P, Xu Tong, Stabile Roberto, Joosten Rosalie, Tucci Francesco A, van Royen Martin, Trerotola Marco, Alberti Saverio, Sacchetti Andrea, Fodde Riccardo
Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy.
iScience. 2024 Aug 5;27(9):110658. doi: 10.1016/j.isci.2024.110658. eCollection 2024 Sep 20.
Intra-tumor heterogeneity, i.e., the presence of diverse cell types and subpopulations within tumors, presents a significant obstacle in cancer treatment due to its negative consequences for resistance to therapy and disease recurrence. However, the mechanisms that underlie intra-tumor heterogeneity and result in the plethora of different cancer cells within a single lesion remain poorly understood. Here, we leverage the SW480 cell line as a model system to investigate the molecular and functional diversity of colon cancer cells. Through a combination of fluorescence-activated cell sorting (FACS) analysis and transcriptomic profiling, we identified three distinct subpopulations, namely resident cancer stem cells (rCSCs), migratory CSCs (mCSCs), and high-relapse cells (HRCs). These subpopulations show varying Wnt signaling levels and gene expression profiles mirroring their stem-like and functional properties. Examination of publicly available spatial transcriptomic data confirms the presence of these subpopulations in patient-derived cancers and reveals their distinct spatial distribution relative to the tumor microenvironment.
肿瘤内异质性，即肿瘤内存在多种细胞类型和亚群，由于其对治疗耐药性和疾病复发产生负面影响，在癌症治疗中构成了重大障碍。然而，肿瘤内异质性背后的机制以及导致单个病灶内存在大量不同癌细胞的原因仍知之甚少。在此，我们利用SW480细胞系作为模型系统，研究结肠癌细胞的分子和功能多样性。通过荧光激活细胞分选（FACS）分析和转录组分析相结合的方法，我们鉴定出三个不同的亚群，即驻留癌干细胞（rCSCs）、迁移性癌干细胞（mCSCs）和高复发细胞（HRCs）。这些亚群显示出不同的Wnt信号水平，其基因表达谱反映了它们的干细胞样和功能特性。对公开可用的空间转录组数据的分析证实了这些亚群在患者来源的癌症中的存在，并揭示了它们相对于肿瘤微环境的独特空间分布。
