Modeling tumor relapse using proliferation tracing and ablation transgenic mouse
Abstract Tumor relapse remains a significant obstacle to successful therapy. Preclinical animal models that accurately reflect tumor relapse in patients are urgently needed. Here, we employed a dual recombinase-mediated genetic system to genetically trace and ablate proliferating cells in a polyomav...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00792-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849234705867603968 |
|---|---|
| author | Chuang Zhao Xin-nan Zheng Han-ying Huang Lin Tian |
| author_facet | Chuang Zhao Xin-nan Zheng Han-ying Huang Lin Tian |
| author_sort | Chuang Zhao |
| collection | DOAJ |
| description | Abstract Tumor relapse remains a significant obstacle to successful therapy. Preclinical animal models that accurately reflect tumor relapse in patients are urgently needed. Here, we employed a dual recombinase-mediated genetic system to genetically trace and ablate proliferating cells in a polyomavirus middle T antigen (PyMT)-induced spontaneous murine breast cancer model. This system enabled the acute ablation of cells that had undergone proliferation within a defined time window, resulting in a drastic tumor shrinkage, followed by a gradual tumor relapse due to the presence of residual low-cycling cells. We then applied single-cell RNA sequencing (scRNA-seq) to unbiasedly compare the tumor ecosystems of the primary and relapsed PyMT tumors. Compared with the primary tumors, the relapsed tumors exhibited a higher proportion of cancer stem cells and pro-tumor γδ T cells, as well as co-expression of Spp1 and Vegfa in multiple myeloid cell populations – features that predict poor therapeutic response and unfavorable outcomes in human breast cancer patients. Collectively, this proliferation tracing and ablation model emulates chemotherapies that preferentially eliminate proliferating cancer cells, serving as a robust tool and a valuable resource for testing novel therapeutic strategies in relapsed tumors. |
| format | Article |
| id | doaj-art-a0562741579f4860b04bb60f44c81dbd |
| 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-a0562741579f4860b04bb60f44c81dbd2025-08-20T04:03:03ZengNature Portfolionpj Breast Cancer2374-46772025-07-0111111210.1038/s41523-025-00792-1Modeling tumor relapse using proliferation tracing and ablation transgenic mouseChuang Zhao0Xin-nan Zheng1Han-ying Huang2Lin Tian3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterAbstract Tumor relapse remains a significant obstacle to successful therapy. Preclinical animal models that accurately reflect tumor relapse in patients are urgently needed. Here, we employed a dual recombinase-mediated genetic system to genetically trace and ablate proliferating cells in a polyomavirus middle T antigen (PyMT)-induced spontaneous murine breast cancer model. This system enabled the acute ablation of cells that had undergone proliferation within a defined time window, resulting in a drastic tumor shrinkage, followed by a gradual tumor relapse due to the presence of residual low-cycling cells. We then applied single-cell RNA sequencing (scRNA-seq) to unbiasedly compare the tumor ecosystems of the primary and relapsed PyMT tumors. Compared with the primary tumors, the relapsed tumors exhibited a higher proportion of cancer stem cells and pro-tumor γδ T cells, as well as co-expression of Spp1 and Vegfa in multiple myeloid cell populations – features that predict poor therapeutic response and unfavorable outcomes in human breast cancer patients. Collectively, this proliferation tracing and ablation model emulates chemotherapies that preferentially eliminate proliferating cancer cells, serving as a robust tool and a valuable resource for testing novel therapeutic strategies in relapsed tumors.https://doi.org/10.1038/s41523-025-00792-1 |
| spellingShingle | Chuang Zhao Xin-nan Zheng Han-ying Huang Lin Tian Modeling tumor relapse using proliferation tracing and ablation transgenic mouse npj Breast Cancer |
| title | Modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| title_full | Modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| title_fullStr | Modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| title_full_unstemmed | Modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| title_short | Modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| title_sort | modeling tumor relapse using proliferation tracing and ablation transgenic mouse |
| url | https://doi.org/10.1038/s41523-025-00792-1 |
| work_keys_str_mv | AT chuangzhao modelingtumorrelapseusingproliferationtracingandablationtransgenicmouse AT xinnanzheng modelingtumorrelapseusingproliferationtracingandablationtransgenicmouse AT hanyinghuang modelingtumorrelapseusingproliferationtracingandablationtransgenicmouse AT lintian modelingtumorrelapseusingproliferationtracingandablationtransgenicmouse |