Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line : = Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line
AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response prediction.METHODS Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid cancers.RESULTS The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018-09-07 2018 |
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| Erschienen: |
2018-09-07 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2018 |
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| Enthalten in: |
World journal of gastroenterology - (2018), 33 vom: 07. Sept., Seite 3749-3759 Original Letters: Enthalten in (DE-576)276271955 (DE-576)276271955 |
| Reihe: |
China Academic Journals (CAJ), E, 医药卫生科技 = Medicine & Public Health |
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| Sprache: |
Chinesisch |
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| Weiterer Titel: |
Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line |
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| Beteiligte Personen: |
Michael Gock [VerfasserIn] |
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| Links: |
oversea.cnki.net [lizenzpflichtig] |
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| Anmerkungen: |
Author info:Michael Gock;Christina S Mullins;Christine Harnack;Friedrich Prall;Robert Ramer;Anja G?der;Oliver H Kr?mer;Ernst Klar;Michael Linnebacher;Department of General Surgery, University of Rostock;Department of General Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock;Institute of Pathology, University of Rostock;Institute of Pharmacology, University of Rostock;Institute of Toxicology,University Medical Center Mainz |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
CAJ60517475X |
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| 245 | 1 | 0 | |a Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line |b = Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line |
| 246 | 3 | 1 | |a Establishment, functional and genetic characterization of a colon derived large cell neuroendocrine carcinoma cell line |
| 264 | 1 | |c 2018-09-07 | |
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| 500 | |a Author info:Michael Gock;Christina S Mullins;Christine Harnack;Friedrich Prall;Robert Ramer;Anja G?der;Oliver H Kr?mer;Ernst Klar;Michael Linnebacher;Department of General Surgery, University of Rostock;Department of General Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock;Institute of Pathology, University of Rostock;Institute of Pharmacology, University of Rostock;Institute of Toxicology,University Medical Center Mainz | ||
| 520 | |a AIM To establish cell line and patient-derived xenograft(PDX) models for neuroendocrine carcinomas(NEC) which is highly desirable for gaining insight into tumor development as well as preclinical research includingbiomarker testing and drug response prediction.METHODS Cell line establishment was conducted from direct in vitro culturing of colonic NEC tissue(HROC57). A PDX could also successfully be established from vitally frozen tumor samples. Morphological features, invasive and migratory behavior of the HROC57 cells as well as expression of neuroendocrine markers were vastly analyzed. Phenotypic analysis was done by microscopy and multicolor flow cytometry. The extensive molecular-pathological profiling included mutation analysis, assessment of chromosomal and microsatellite instability; and in addition, fingerprinting(i.e., STR analysis) was performed from the cell line in direct comparison to primary patient-derived tissues and the PDX model established. Drug responsiveness was examined for a panel of chemotherapeutics in clinical use for the treatment of solid cancers.RESULTS The established cell line HROC57 showed distinct morphological and molecular features of a poorly differentiated large-cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a Cp G island promoter methylation positive cell line with microsatellite instability being absent. The following mutation profile was observed: KRAS(wt), BRAF(mut). A high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it was more resistant towards rapamycin. CONCLUSION We successfully established and characterized a novel patient-derived NEC cell line in parallel to a PDX model as a useful tool for further analysis of the biological characteristics and for development of novel diagnostic and therapeutic options for NEC. | ||
| 610 | 2 | 4 | |a Department of General Surgery, University of Rostock |
| 610 | 2 | 4 | |a Department of General Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock |
| 610 | 2 | 4 | |a Institute of Pathology, University of Rostock |
| 610 | 2 | 4 | |a Institute of Pharmacology, University of Rostock |
| 610 | 2 | 4 | |a Institute of Toxicology,University Medical Center Mainz |
| 650 | 4 | |a 神经系肿瘤 | |
| 650 | 4 | |a 肿瘤学 | |
| 650 | 4 | |a 医药、卫生 | |
| 650 | 4 | |a Neurology | |
| 650 | 4 | |a Oncology | |
| 650 | 4 | |a 医药卫生科技 | |
| 650 | 4 | |a Medicine & Public Health | |
| 650 | 4 | |a Patient-derived tumor model | |
| 650 | 4 | |a Large cell neuroendocrine carcinoma | |
| 650 | 4 | |a Individualized medicine | |
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| 700 | 0 | |a Christine Harnack |4 oth | |
| 700 | 0 | |a Friedrich Prall |4 oth | |
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| 700 | 0 | |a Anja G?der |4 oth | |
| 700 | 0 | |a Oliver H Kr?mer |4 oth | |
| 700 | 0 | |a Ernst Klar |4 oth | |
| 700 | 0 | |a Michael Linnebacher |4 oth | |
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