Application of an Integrated Single-Cell and Three-Dimensional Spheroid Culture Platform for Investigating Drug Resistance Heterogeneity and Epithelial–Mesenchymal Transition (EMT) in Lung Cancer Subclones DOI Open Access

Shin-Hu Chen,

Jian-Hong Yu,

Yu‐Chun Lin

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1766 - 1766

Опубликована: Фев. 19, 2025

Lung cancer is a leading cause of cancer-related mortality worldwide, largely due to its heterogeneity and intrinsic drug resistance. Malignant pleural effusions (MPEs) provide diverse tumor cell populations ideal for studying these complexities. Although chemotherapy targeted therapies can be initially effective, subpopulations cells with phenotypic plasticity often survive treatment, eventually developing Here, we integrated single-cell isolation three-dimensional (3D) spheroid culture dissect subclonal responses, aiming inform precision medicine approaches. Using A549 lung cells, established cisplatin-resistant line isolated three resistant subclones (Holoclone, Meroclone, Paraclone) via sorting. In 3D spheroids, Docetaxel Alimta displayed higher IC50 values than in 2D cultures, suggesting that models better reflect clinical dosing. Additionally, MPE-derived Holoclone Paraclone exhibited distinct sensitivities Giotrif Capmatinib, revealing their heterogeneous responses. Molecular analyses confirmed elevated ABCB1, ABCG2, stem (CSC) markers (OCT4, SOX2, CD44, CD133), epithelial-mesenchymal transition (EMT) (E-cadherin downregulation, increased Vimentin, N-cadherin, Twist) subclones, correlating enhanced migration invasion. This approach clarifies the interplay between heterogeneity, CSC/EMT phenotypes, resistance, providing valuable tool predicting therapeutic responses guiding personalized, combination-based treatments.

Язык: Английский

Application of an Integrated Single-Cell and Three-Dimensional Spheroid Culture Platform for Investigating Drug Resistance Heterogeneity and Epithelial–Mesenchymal Transition (EMT) in Lung Cancer Subclones DOI Open Access

Shin-Hu Chen,

Jian-Hong Yu,

Yu‐Chun Lin

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1766 - 1766

Опубликована: Фев. 19, 2025

Lung cancer is a leading cause of cancer-related mortality worldwide, largely due to its heterogeneity and intrinsic drug resistance. Malignant pleural effusions (MPEs) provide diverse tumor cell populations ideal for studying these complexities. Although chemotherapy targeted therapies can be initially effective, subpopulations cells with phenotypic plasticity often survive treatment, eventually developing Here, we integrated single-cell isolation three-dimensional (3D) spheroid culture dissect subclonal responses, aiming inform precision medicine approaches. Using A549 lung cells, established cisplatin-resistant line isolated three resistant subclones (Holoclone, Meroclone, Paraclone) via sorting. In 3D spheroids, Docetaxel Alimta displayed higher IC50 values than in 2D cultures, suggesting that models better reflect clinical dosing. Additionally, MPE-derived Holoclone Paraclone exhibited distinct sensitivities Giotrif Capmatinib, revealing their heterogeneous responses. Molecular analyses confirmed elevated ABCB1, ABCG2, stem (CSC) markers (OCT4, SOX2, CD44, CD133), epithelial-mesenchymal transition (EMT) (E-cadherin downregulation, increased Vimentin, N-cadherin, Twist) subclones, correlating enhanced migration invasion. This approach clarifies the interplay between heterogeneity, CSC/EMT phenotypes, resistance, providing valuable tool predicting therapeutic responses guiding personalized, combination-based treatments.

Язык: Английский

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