Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity
IntroductionFor pre-clinical drug development and precision oncology research, robust cancer cell models are essential. Patient-derived models in low passages retain more genetic and phenotypic characteristics of their original tumors than conventional cancer cell lines. Subentity, individual geneti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1089681/full |
| _version_ | 1797830908200353792 |
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| author | Ingo Andus Friedrich Prall Michael Linnebacher Christina S. Linnebacher |
| author_facet | Ingo Andus Friedrich Prall Michael Linnebacher Christina S. Linnebacher |
| author_sort | Ingo Andus |
| collection | DOAJ |
| description | IntroductionFor pre-clinical drug development and precision oncology research, robust cancer cell models are essential. Patient-derived models in low passages retain more genetic and phenotypic characteristics of their original tumors than conventional cancer cell lines. Subentity, individual genetics, and heterogeneity greatly influence drug sensitivity and clinical outcome.Materials and methodsHere, we report on the establishment and characterization of three patient-derived cell lines (PDCs) of different subentities of non-small cell lung cancer (NSCLC): adeno-, squamous cell, and pleomorphic carcinoma. The in-depth characterization of our PDCs included phenotype, proliferation, surface protein expression, invasion, and migration behavior as well as whole-exome and RNA sequencing. Additionally, in vitro drug sensitivity towards standard-of-care chemotherapeutic regimens was evaluated.ResultsThe pathological and molecular properties of the patients’ tumors were preserved in the PDC models HROLu22, HROLu55, and HROBML01. All cell lines expressed HLA I, while none were positive for HLA II. The epithelial cell marker CD326 and the lung tumor markers CCDC59, LYPD3, and DSG3 were also detected. The most frequently mutated genes included TP53, MXRA5, MUC16, and MUC19. Among the most overexpressed genes in tumor cells compared to normal tissue were the transcription factors HOXB9, SIM2, ZIC5, SP8, TFAP2A, FOXE1, HOXB13, and SALL4; the cancer testis antigen CT83; and the cytokine IL23A. The most downregulated genes on the RNA level encode the long non-coding RNA LANCL1-AS1, LINC00670, BANCR, and LOC100652999; the regulator of angiogenesis ANGPT4; the signaling molecules PLA2G1B and RS1; and the immune modulator SFTPD. Furthermore, neither pre-existing therapy resistances nor drug antagonistic effects could be observed.ConclusionIn summary, we successfully established three novel NSCLC PDC models from an adeno-, a squamous cell, and a pleomorphic carcinoma. Of note, NSCLC cell models of the pleomorphic subentity are very rare. The detailed characterization including molecular, morphological, and drug-sensitivity profiling makes these models valuable pre-clinical tools for drug development applications and research on precision cancer therapy. The pleomorphic model additionally enables research on a functional and cell-based level of this rare NCSLC subentity. |
| first_indexed | 2024-04-09T13:43:50Z |
| format | Article |
| id | doaj.art-3c949a7c8315404f9adeae33ce05800b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T13:43:50Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3c949a7c8315404f9adeae33ce05800b2023-05-09T05:43:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.10896811089681Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentityIngo Andus0Friedrich Prall1Michael Linnebacher2Christina S. Linnebacher3Patient Models for Precision Medicine, Department of General Surgery, University Medical Center Rostock, Rostock, GermanyInstitute of Pathology, University Medical Center Rostock, Rostock, GermanyMolecular Oncology and Immunotherapy, Department of General Surgery, University Medical Center Rostock, Rostock, GermanyPatient Models for Precision Medicine, Department of General Surgery, University Medical Center Rostock, Rostock, GermanyIntroductionFor pre-clinical drug development and precision oncology research, robust cancer cell models are essential. Patient-derived models in low passages retain more genetic and phenotypic characteristics of their original tumors than conventional cancer cell lines. Subentity, individual genetics, and heterogeneity greatly influence drug sensitivity and clinical outcome.Materials and methodsHere, we report on the establishment and characterization of three patient-derived cell lines (PDCs) of different subentities of non-small cell lung cancer (NSCLC): adeno-, squamous cell, and pleomorphic carcinoma. The in-depth characterization of our PDCs included phenotype, proliferation, surface protein expression, invasion, and migration behavior as well as whole-exome and RNA sequencing. Additionally, in vitro drug sensitivity towards standard-of-care chemotherapeutic regimens was evaluated.ResultsThe pathological and molecular properties of the patients’ tumors were preserved in the PDC models HROLu22, HROLu55, and HROBML01. All cell lines expressed HLA I, while none were positive for HLA II. The epithelial cell marker CD326 and the lung tumor markers CCDC59, LYPD3, and DSG3 were also detected. The most frequently mutated genes included TP53, MXRA5, MUC16, and MUC19. Among the most overexpressed genes in tumor cells compared to normal tissue were the transcription factors HOXB9, SIM2, ZIC5, SP8, TFAP2A, FOXE1, HOXB13, and SALL4; the cancer testis antigen CT83; and the cytokine IL23A. The most downregulated genes on the RNA level encode the long non-coding RNA LANCL1-AS1, LINC00670, BANCR, and LOC100652999; the regulator of angiogenesis ANGPT4; the signaling molecules PLA2G1B and RS1; and the immune modulator SFTPD. Furthermore, neither pre-existing therapy resistances nor drug antagonistic effects could be observed.ConclusionIn summary, we successfully established three novel NSCLC PDC models from an adeno-, a squamous cell, and a pleomorphic carcinoma. Of note, NSCLC cell models of the pleomorphic subentity are very rare. The detailed characterization including molecular, morphological, and drug-sensitivity profiling makes these models valuable pre-clinical tools for drug development applications and research on precision cancer therapy. The pleomorphic model additionally enables research on a functional and cell-based level of this rare NCSLC subentity.https://www.frontiersin.org/articles/10.3389/fonc.2023.1089681/fullpatient-derived cell lines (PDC)lung tumorsnon-small cell lung cancer (NSCLC)in vitro therapy responsepatient-individual tumor models |
| spellingShingle | Ingo Andus Friedrich Prall Michael Linnebacher Christina S. Linnebacher Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity Frontiers in Oncology patient-derived cell lines (PDC) lung tumors non-small cell lung cancer (NSCLC) in vitro therapy response patient-individual tumor models |
| title | Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity |
| title_full | Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity |
| title_fullStr | Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity |
| title_full_unstemmed | Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity |
| title_short | Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity |
| title_sort | establishment characterization and drug screening of low passage patient individual non small cell lung cancer in vitro models including the rare pleomorphic subentity |
| topic | patient-derived cell lines (PDC) lung tumors non-small cell lung cancer (NSCLC) in vitro therapy response patient-individual tumor models |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1089681/full |
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