A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/15/2264 |
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| author | Céline Hervieu Mireille Verdier Elodie Barthout Gaëlle Bégaud Niki Christou Magali Sage Julie Pannequin Serge Battu Muriel Mathonnet |
| author_facet | Céline Hervieu Mireille Verdier Elodie Barthout Gaëlle Bégaud Niki Christou Magali Sage Julie Pannequin Serge Battu Muriel Mathonnet |
| author_sort | Céline Hervieu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:31:52Z |
| format | Article |
| id | doaj.art-04bb957d97ab4d3b96028f90f2d27d44 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:31:52Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-04bb957d97ab4d3b96028f90f2d27d442023-12-03T12:31:43ZengMDPI AGCells2073-44092022-07-011115226410.3390/cells11152264A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to TherapiesCéline Hervieu0Mireille Verdier1Elodie Barthout2Gaëlle Bégaud3Niki Christou4Magali Sage5Julie Pannequin6Serge Battu7Muriel Mathonnet8UMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceBISCEm US42 INSERM-UAR 2015 CNRS “Integrative Biology Health Chemistry Environment”, Ω-Health Institute, 87025 Limoges, FranceUMR 5203 CNRS-INSERM, Institute of Functional Genomics, University of Montpellier, 34094 Montpellier, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceUMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, FranceCancer 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.https://www.mdpi.com/2073-4409/11/15/2264cancer stem cellscolorectal cancerlabel-free cell sortingchemoresistanceintratumoral cellular heterogeneity |
| spellingShingle | Céline Hervieu Mireille Verdier Elodie Barthout Gaëlle Bégaud Niki Christou Magali Sage Julie Pannequin Serge Battu Muriel Mathonnet A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies Cells cancer stem cells colorectal cancer label-free cell sorting chemoresistance intratumoral cellular heterogeneity |
| title | A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies |
| title_full | A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies |
| title_fullStr | A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies |
| title_full_unstemmed | A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies |
| title_short | A Label-Free Cell Sorting Approach to Highlight the Impact of Intratumoral Cellular Heterogeneity and Cancer Stem Cells on Response to Therapies |
| title_sort | label free cell sorting approach to highlight the impact of intratumoral cellular heterogeneity and cancer stem cells on response to therapies |
| topic | cancer stem cells colorectal cancer label-free cell sorting chemoresistance intratumoral cellular heterogeneity |
| url | https://www.mdpi.com/2073-4409/11/15/2264 |
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