Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma
Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammat...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-05-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0752-0 |
| _version_ | 1818966506773413888 |
|---|---|
| author | Yeonhwa Song Jin-Sun Kim Se-Hyuk Kim Yoon Kyung Park Eunsil Yu Ki-Hun Kim Eul-Ju Seo Heung-Bum Oh Han Chu Lee Kang Mo Kim Haeng Ran Seo |
| author_facet | Yeonhwa Song Jin-Sun Kim Se-Hyuk Kim Yoon Kyung Park Eunsil Yu Ki-Hun Kim Eul-Ju Seo Heung-Bum Oh Han Chu Lee Kang Mo Kim Haeng Ran Seo |
| author_sort | Yeonhwa Song |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients. Methods Based on these two new HCC cell lines, we have developed chemosensitivity assays for patient-derived multicellular tumor spheroids (MCTSs) in order to select optimized anti-cancer drugs to provide more informative data for clinical drug application. To monitor the effect of the interaction of cancer cells and stromal cells in MCTS, we used a 3D co-culture model with patient-derived HCC cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy. Results To validate our system, we performed a comparison of chemosensitivity of the three culture systems, which are monolayer culture system, tumor spheroids, and MCTSs of patient-derived cells, to sorafenib, 5-fluorouracil, and cisplatin, as these compounds are typically standard therapy for advanced HCC in South Korea. Conclusion In summary, these findings suggest that the MCTS culture system is the best methodology for screening for optimized treatment for each patients with HCC, because tumor spheroids not only mirror the 3D cellular context of the tumors but also exhibit therapeutically relevant pathophysiological gradients and heterogeneity of in vivo tumors. |
| first_indexed | 2024-12-20T13:33:59Z |
| format | Article |
| id | doaj.art-fa10a60671f847108d40127210cb18b6 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-20T13:33:59Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-fa10a60671f847108d40127210cb18b62022-12-21T19:39:01ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-05-0137111310.1186/s13046-018-0752-0Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinomaYeonhwa Song0Jin-Sun Kim1Se-Hyuk Kim2Yoon Kyung Park3Eunsil Yu4Ki-Hun Kim5Eul-Ju Seo6Heung-Bum Oh7Han Chu Lee8Kang Mo Kim9Haeng Ran Seo10Cancer Biology Research Laboratory, Institut Pasteur KoreaDivision of Gastroenterology and Hepatology, ASAN Medical centerCancer Biology Research Laboratory, Institut Pasteur KoreaDivision of Gastroenterology and Hepatology, ASAN Medical centerDepartment of Pathology, University of Ulsan College of MedicineDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Ulsan College of MedicineDepartment of Laboratory Medicine, Asan Medical, Center, University of Ulsan College of MedicineDepartment of Laboratory Medicine, Asan Medical, Center, University of Ulsan College of MedicineDivision of Gastroenterology and Hepatology, ASAN Medical centerDivision of Gastroenterology and Hepatology, ASAN Medical centerCancer Biology Research Laboratory, Institut Pasteur KoreaAbstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients. Methods Based on these two new HCC cell lines, we have developed chemosensitivity assays for patient-derived multicellular tumor spheroids (MCTSs) in order to select optimized anti-cancer drugs to provide more informative data for clinical drug application. To monitor the effect of the interaction of cancer cells and stromal cells in MCTS, we used a 3D co-culture model with patient-derived HCC cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy. Results To validate our system, we performed a comparison of chemosensitivity of the three culture systems, which are monolayer culture system, tumor spheroids, and MCTSs of patient-derived cells, to sorafenib, 5-fluorouracil, and cisplatin, as these compounds are typically standard therapy for advanced HCC in South Korea. Conclusion In summary, these findings suggest that the MCTS culture system is the best methodology for screening for optimized treatment for each patients with HCC, because tumor spheroids not only mirror the 3D cellular context of the tumors but also exhibit therapeutically relevant pathophysiological gradients and heterogeneity of in vivo tumors.http://link.springer.com/article/10.1186/s13046-018-0752-0Hepatocellular carcinoma (HCC)Multicellular tumor spheroids (MCTS)Optimized treatmentMCTS-based chemosensitivity assays |
| spellingShingle | Yeonhwa Song Jin-Sun Kim Se-Hyuk Kim Yoon Kyung Park Eunsil Yu Ki-Hun Kim Eul-Ju Seo Heung-Bum Oh Han Chu Lee Kang Mo Kim Haeng Ran Seo Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma Journal of Experimental & Clinical Cancer Research Hepatocellular carcinoma (HCC) Multicellular tumor spheroids (MCTS) Optimized treatment MCTS-based chemosensitivity assays |
| title | Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| title_full | Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| title_fullStr | Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| title_full_unstemmed | Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| title_short | Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| title_sort | patient derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma |
| topic | Hepatocellular carcinoma (HCC) Multicellular tumor spheroids (MCTS) Optimized treatment MCTS-based chemosensitivity assays |
| url | http://link.springer.com/article/10.1186/s13046-018-0752-0 |
| work_keys_str_mv | AT yeonhwasong patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT jinsunkim patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT sehyukkim patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT yoonkyungpark patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT eunsilyu patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT kihunkim patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT euljuseo patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT heungbumoh patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT hanchulee patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT kangmokim patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma AT haengranseo patientderivedmulticellulartumorspheroidstowardsoptimizedtreatmentforpatientswithhepatocellularcarcinoma |