Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer
Abstract Triple-negative breast cancer (TNBC) is associated with poor prognosis and high recurrence, driven by residual tumor cells that survive chemotherapy. To monitor therapy response in vivo, we established a clinically relevant TAC regimen (docetaxel, doxorubicin, cyclophosphamide) in mice bear...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00795-y |
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| author | Silvia Steinbauer Jamie D. Cowles Mohammad Ali Sabbaghi Marle Poppelaars Azaz Hussain Marina Wagesreither Daniela Laimer-Gruber Jozsef Tovari Gergely Szakacs Agnes Csiszar |
| author_facet | Silvia Steinbauer Jamie D. Cowles Mohammad Ali Sabbaghi Marle Poppelaars Azaz Hussain Marina Wagesreither Daniela Laimer-Gruber Jozsef Tovari Gergely Szakacs Agnes Csiszar |
| author_sort | Silvia Steinbauer |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) is associated with poor prognosis and high recurrence, driven by residual tumor cells that survive chemotherapy. To monitor therapy response in vivo, we established a clinically relevant TAC regimen (docetaxel, doxorubicin, cyclophosphamide) in mice bearing mammary tumors derived from K14cre;Brca1 F/F ;Trp53 F/F (KB1P) organoids expressing an mCherry-AkaLuc dual reporter (mCA-KB1P). AkaLuc bioluminescence imaging (AkaBLI) enabled non-invasive detection of minimal residual disease (MRD) with a sensitivity of approximately 1000 cells. As AkaLuc elicited an immune response, we generated Histon2B-mCherry-expressing KB1P organoids (HmC-KB1P) to study tumor cell survival in immunocompetent hosts. Flow cytometry and histological analysis revealed that MRD in immunocompetent mice is characterized by few residual cells with transient loss of epithelial markers, in contrast to immunodeficient hosts, which retains more epithelial-like cells. These findings validate AkaBLI for sensitive MRD detection and highlight the immune system’s critical role in modulating residual tumor cell fate following chemotherapy. |
| format | Article |
| id | doaj-art-ebe0f390b83f42cc91c40e0e78a7c7e9 |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-ebe0f390b83f42cc91c40e0e78a7c7e92025-08-20T03:43:20ZengNature Portfolionpj Breast Cancer2374-46772025-07-0111111310.1038/s41523-025-00795-yEnhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancerSilvia Steinbauer0Jamie D. Cowles1Mohammad Ali Sabbaghi2Marle Poppelaars3Azaz Hussain4Marina Wagesreither5Daniela Laimer-Gruber6Jozsef Tovari7Gergely Szakacs8Agnes Csiszar9Center for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaDepartment of Biomedical Imaging and Image-Guided Therapy, Division of Structural and Molecular Preclinical Imaging, Medical University of ViennaDepartment of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of OncologyCenter for Cancer Research, Medical University of ViennaCenter for Cancer Research, Medical University of ViennaAbstract Triple-negative breast cancer (TNBC) is associated with poor prognosis and high recurrence, driven by residual tumor cells that survive chemotherapy. To monitor therapy response in vivo, we established a clinically relevant TAC regimen (docetaxel, doxorubicin, cyclophosphamide) in mice bearing mammary tumors derived from K14cre;Brca1 F/F ;Trp53 F/F (KB1P) organoids expressing an mCherry-AkaLuc dual reporter (mCA-KB1P). AkaLuc bioluminescence imaging (AkaBLI) enabled non-invasive detection of minimal residual disease (MRD) with a sensitivity of approximately 1000 cells. As AkaLuc elicited an immune response, we generated Histon2B-mCherry-expressing KB1P organoids (HmC-KB1P) to study tumor cell survival in immunocompetent hosts. Flow cytometry and histological analysis revealed that MRD in immunocompetent mice is characterized by few residual cells with transient loss of epithelial markers, in contrast to immunodeficient hosts, which retains more epithelial-like cells. These findings validate AkaBLI for sensitive MRD detection and highlight the immune system’s critical role in modulating residual tumor cell fate following chemotherapy.https://doi.org/10.1038/s41523-025-00795-y |
| spellingShingle | Silvia Steinbauer Jamie D. Cowles Mohammad Ali Sabbaghi Marle Poppelaars Azaz Hussain Marina Wagesreither Daniela Laimer-Gruber Jozsef Tovari Gergely Szakacs Agnes Csiszar Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer npj Breast Cancer |
| title | Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer |
| title_full | Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer |
| title_fullStr | Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer |
| title_full_unstemmed | Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer |
| title_short | Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer |
| title_sort | enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple negative breast cancer |
| url | https://doi.org/10.1038/s41523-025-00795-y |
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