5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information
Abstract Background Colorectal cancer is a commonly diagnosed cancer worldwide. Unfortunately, many patients do not respond to standard chemotherapy treatments and develop disease relapse and metastases. Besides cancer cell specific genetic changes, heterogeneity in the tumor microenvironment contri...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03423-6 |
| _version_ | 1818008259853811712 |
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| author | Simona Salerno Anders Ståhlberg André Holdfeldt Elinor Bexe Lindskog Göran Landberg |
| author_facet | Simona Salerno Anders Ståhlberg André Holdfeldt Elinor Bexe Lindskog Göran Landberg |
| author_sort | Simona Salerno |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer is a commonly diagnosed cancer worldwide. Unfortunately, many patients do not respond to standard chemotherapy treatments and develop disease relapse and metastases. Besides cancer cell specific genetic changes, heterogeneity in the tumor microenvironment contribute to the clinical presentation of the disease and can potentially also influence drug resistance. By using a recently developed patient-derived scaffold method monitoring how a standardized reporter cancer cell line adapts to various microenvironments treated with chemotherapy, we wanted to clarify how individual patient specific microenvironments influence the chemotherapy response in colorectal cancer. Methods Surgically resected colorectal cancer specimens from 89 patients were decellularized to produce patient-derived scaffold, which were seeded with HT29 cells, cultured for 3 weeks, and treated with 5-fluorouracil. Gene expression changes of adapted and treated HT29 cells were monitored by qPCR and compared with clinical parameters including disease-free survival. Results The effects of 5-fluorouracil treatment varied between different patient-derived scaffold, but generally induced a reduced expression of proliferation genes and increased expression of pluripotency and epithelial-to-mesenchymal transition genes. Interestingly, patient-derived scaffold cultures obtained from patients with disease recurrences showed a significantly less pronounced anti-proliferative effect of 5-fluorouracil and more pronounced increase of pluripotency, with MKI67 and POU5F1 being among the most significant genes linked to disease relapse in colorectal cancer. Conclusions Colorectal patient-derived scaffold can decode clinically relevant tumor microenvironmental influence of 5-fluorouracil treatment effects opening up for optimized precision medicine in colorectal cancer treatment. |
| first_indexed | 2024-04-14T05:26:50Z |
| format | Article |
| id | doaj.art-12ec8eec840f487d88f7ff1809da12cb |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-14T05:26:50Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-12ec8eec840f487d88f7ff1809da12cb2022-12-22T02:09:56ZengBMCJournal of Translational Medicine1479-58762022-05-0120111310.1186/s12967-022-03423-65-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical informationSimona Salerno0Anders Ståhlberg1André Holdfeldt2Elinor Bexe Lindskog3Göran Landberg4Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy at University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy at University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy at University of GothenburgDepartment of Surgery, Region Västra Götaland, Sahlgrenska University HospitalDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy at University of GothenburgAbstract Background Colorectal cancer is a commonly diagnosed cancer worldwide. Unfortunately, many patients do not respond to standard chemotherapy treatments and develop disease relapse and metastases. Besides cancer cell specific genetic changes, heterogeneity in the tumor microenvironment contribute to the clinical presentation of the disease and can potentially also influence drug resistance. By using a recently developed patient-derived scaffold method monitoring how a standardized reporter cancer cell line adapts to various microenvironments treated with chemotherapy, we wanted to clarify how individual patient specific microenvironments influence the chemotherapy response in colorectal cancer. Methods Surgically resected colorectal cancer specimens from 89 patients were decellularized to produce patient-derived scaffold, which were seeded with HT29 cells, cultured for 3 weeks, and treated with 5-fluorouracil. Gene expression changes of adapted and treated HT29 cells were monitored by qPCR and compared with clinical parameters including disease-free survival. Results The effects of 5-fluorouracil treatment varied between different patient-derived scaffold, but generally induced a reduced expression of proliferation genes and increased expression of pluripotency and epithelial-to-mesenchymal transition genes. Interestingly, patient-derived scaffold cultures obtained from patients with disease recurrences showed a significantly less pronounced anti-proliferative effect of 5-fluorouracil and more pronounced increase of pluripotency, with MKI67 and POU5F1 being among the most significant genes linked to disease relapse in colorectal cancer. Conclusions Colorectal patient-derived scaffold can decode clinically relevant tumor microenvironmental influence of 5-fluorouracil treatment effects opening up for optimized precision medicine in colorectal cancer treatment.https://doi.org/10.1186/s12967-022-03423-6Colorectal cancerPatient-derived scaffoldDecellularized matrix5-fluorouracilDrug screening |
| spellingShingle | Simona Salerno Anders Ståhlberg André Holdfeldt Elinor Bexe Lindskog Göran Landberg 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information Journal of Translational Medicine Colorectal cancer Patient-derived scaffold Decellularized matrix 5-fluorouracil Drug screening |
| title | 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information |
| title_full | 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information |
| title_fullStr | 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information |
| title_full_unstemmed | 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information |
| title_short | 5-fluorouracil treatment of patient-derived scaffolds from colorectal cancer reveal clinically critical information |
| title_sort | 5 fluorouracil treatment of patient derived scaffolds from colorectal cancer reveal clinically critical information |
| topic | Colorectal cancer Patient-derived scaffold Decellularized matrix 5-fluorouracil Drug screening |
| url | https://doi.org/10.1186/s12967-022-03423-6 |
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