An optimized method to culture human primary lung tumor cell spheroids

Article Article scientifique Article An optimized method to culture human primary lung tumor cell spheroids eng 2023-11-25 2023-11-25 author Mueggler Amanda Lorena Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 807039 author Pilotto Eléa Gabriella Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 822024 author Perriraz-Mayer Nadja Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 89157 Département de chirurgie (CHIRU) author Jiang Sicong 0009-0005-2508-2115 Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 969454 author Addeo Alfredo 0000-0003-0988-0828 Department of Oncology, Geneva University Hospitals, 1205 Geneva, Switzerland. 912644 Département de médecine (DEMED) author Bedat Benoît 0000-0002-3758-7867 Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 565412 author Karenovics Wolfram Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 501317 author Triponez Frédéric 0000-0001-7808-496X Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 28673 Département de chirurgie (CHIRU) author Serre Beinier Véronique 0000-0002-6016-1645 Division of Thoracic and Endocrine Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland. 123229 5576 10.3390/cancers15235576 38067281 2072-6694 PMC10705303 https://www.mdpi.com/2072-6694/15/23/5576 Lung cancer is the leading cause of cancer mortality worldwide, with a median survival rate at 5 years of less than 20%. While molecular mapping aids in selecting appropriate therapies, it cannot predict personalized treatment response and long-term efficacy. For addressing these challenges, there is a great need for functional tests. Within this context, we developed patient-derived spheroids (PDS) from tumor and adjacent normal tissue to biomimic the respective tissue for assessing the personalized drug treatment response in vitro. Surgically resected lung specimens were used to generate spheroids using a two-step culture procedure. Flow cytometry and immune staining enabled the characterization of different cell populations resulting from the lung samples. PDS phenotype, cell proliferation and apoptosis were evaluated. Differential gene expression between tumor and adjacent normal tissue was analyzed via RT-qPCR. PDS drug sensitivity was assessed using a cell metabolic assay in response to two chemotherapeutic drug combinations. Cellular and molecular analysis revealed the proportion of epithelial cells, fibroblasts, and immune cells in the patients' tissue samples. Subsequently, PDS models from tumor and normal lung were successfully established using the expanded epithelial cells. As a proof of concept, an analysis of the drug treatment using PDS of lung adenoid cystic carcinoma exhibited a dose-dependent effect in response to cisplatin/etoposide and cisplatin/paclitaxel. Our spheroid model of both tumor and non-tumor lung cells holds great promise for enhancing the treatment efficacy in the cancer patients. Drug screening Drug sensitivity Lung cancer Patient-derived spheroid Dewey 616 Dewey 617 57 Département de chirurgie 222 56 Département de médecine 221 false 902 Cancer du poumon et mésothéliome pleural malin 944 Cancers 15 23 1ac74338-4d9e-4765-9905-2fe5384f7088 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 3985706 application/pdf CC BY-4.0 100e69e821d47b4bc6bd5e8a80d50a1ef8231180560ccb19eb1dda81f48a1956 772bbe53-dcd3-4ef8-b2ef-83a4e19c8c08 Supplemental data Public cancers-15-05576-s001.zip 919772 application/zip db9dfe7ab91a71072491bdc9d4e3685389b61eb72e066266a55ec18bcab2437e openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Year	Views	Downloads

An optimized method to culture human primary lung tumor cell spheroids	Cancers	2023	123	65
L’élaboration de sphéroïdes tumoraux, première étape vers un modèle pré-clinique personnalisé de cancers pulmonaire		2021	75	2

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Mueggler, Amanda Lorena