Treitschke, Steffi and Weidele, Kathrin and Varadarajan, Adithi Ravikumar and Feliciello, Giancarlo and Warfsmann, Jens and Vorbeck, Sybille and Polzer, Bernhard and Botteron, Catherine and Hoffmann, Martin and Dechand, Vadim and Mederer, Tobias and Weber, Florian and Werner-Klein, Melanie and Robold, Tobias and Hofmann, Hans-Stefan and Werno, Christian and Klein, Christoph A. (2023) Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression. INTERNATIONAL JOURNAL OF CANCER, 153 (10). pp. 1854-1867. ISSN 0020-7136, 1097-0215
Full text not available from this repository. (Request a copy)Abstract
The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection. We therefore used ex vivo sphere formation for functional detection of candidate metastasis founders. We generated cell suspensions from 199 LN samples of 131 lung cancer patients and placed them into non-adherent cell culture. Sphere formation was associated with detection of DCCs using EpCAM immunocytology and with significantly poorer prognosis. The prognostic impact of sphere formation was strongly associated with high numbers of EpCAM-positive DCCs and aberrant genotypes of expanded spheres. We also noted sphere formation in patients with no evidence of lymphatic spread, however such spheres showed infrequent expression of signature genes associated with spheres from EpCAM-positive samples and displayed neither typical lung cancer mutations (KRAS, TP53, ERBB1) nor copy number variations, but might be linked to disease progression >5 years post curative surgery. We conclude that EpCAM identifies relevant disease-driving DCCs, that such cells can be expanded for model generation and that further research is needed to clarify the functional and prognostic role of rare EpCAM-negative sphere forming cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DISSEMINATED TUMOR-CELLS; BONE-MARROW; PROGNOSTIC IMPACT; SURVIVAL; GENOME; TRANSCRIPTOME; STATISTICS; disseminated cancer cells; lung cancer; metastatic precursor cells; sphere culture |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Thoraxchirurgie Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Mar 2024 15:10 |
| Last Modified: | 07 Mar 2024 15:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58950 |
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