UMR INSERM 1308-CAPTuR "Control of Cell Activation in Tumor Progression and Therapeutic Resistance", Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, France.
Department of General, Endocrine and Digestive Surgery, University Hospital of Limoges, 87025 Limoges, France.
Cells. 2022 Jul 22;11(15):2264. doi: 10.3390/cells11152264.
Cancer stem cells play a crucial role in tumor initiation, metastasis, and resistance to treatment. Cellular heterogeneity and plasticity complicate the isolation of cancer stem cells. The impact of intra-tumor cellular heterogeneity using a label-free approach remains understudied in the context of treatment resistance. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three sorted cell subpopulations exhibits characteristics of cancer stem cells, including high tumorigenicity in vivo and a higher frequency of tumor-initiating cells compared to the other subpopulations. Due to its chemoresistance, two- and three-dimensional in vitro chemosensitivity assays highlight the therapeutic relevance of this cancer stem cell subpopulation. Thus, our results reveal the major implication of intra-tumor cellular heterogeneity, including cancer stem cells in treatment resistance, thanks to our label-free cell sorting approach. This approach enables-by breaking down the tumor-the study the individualized response of each sorted tumor cell subpopulation and to identify chemoresistance, thus offering new perspectives for personalized therapy.
癌症干细胞在肿瘤的起始、转移和治疗耐药中起着至关重要的作用。细胞异质性和可塑性使癌症干细胞的分离复杂化。在治疗耐药的背景下，使用无标记方法研究肿瘤内细胞异质性对其影响仍不够深入。在这里，我们使用沉降场流分离技术，根据其生物物理特性，无需标记，即可分离结直肠癌细胞系和原代培养物的细胞亚群。三种分选的细胞亚群之一表现出癌症干细胞的特征，包括体内高致瘤性和比其他亚群更高的肿瘤起始细胞频率。由于其化学抗性，二维和三维体外药敏试验突出了这种癌症干细胞亚群的治疗相关性。因此，我们的结果揭示了肿瘤内细胞异质性的主要意义，包括癌症干细胞在治疗耐药性中的作用，这要归功于我们的无标记细胞分选方法。这种方法通过分解肿瘤，使每个分选的肿瘤细胞亚群的个体化反应得以研究，并识别化学耐药性，从而为个性化治疗提供了新的视角。
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