Atrophied thymus can serve as a tumor reservoir for harboring melanoma cells
| dc.contributor.author | Kuriatnikov, Denis | |
| dc.contributor.author | Su, Dong-Ming | |
| dc.creator | Sizova, Olga | |
| dc.creator.orcid | 0000-0003-3441-9064 (Sizova, Olga) | en_US |
| dc.date.accessioned | 2019-08-22T20:10:46Z | |
| dc.date.available | 2019-08-22T20:10:46Z | |
| dc.date.issued | 2018-03-14 | |
| dc.date.submitted | 2018-01-11T09:21:17-08:00 | |
| dc.description | Research Appreciation Day Award Winner - 2018 Quest Diagnostics, Quest Diagnostics 2018 Research Award | |
| dc.description.abstract | Purpose: Tumor metastatic relapse is responsible for main cancer associated mortality and potentially arises from the undetectable minimal number of tumor cells, which are able to resist radio-chemotherapy at a dormant state hiding in certain organs (termed: tumor reservoirs). The largest T-lymphoid organ, the thymus, has been suggested as this kind of pre-metastatic tumor reservoir for B-lymphoma cells. It remains unknown whether the thymus is able to harbor non-lymphoid solid tumor cells, why chemotherapy cannot thoroughly eliminate cancer cells in the thymus, and what the state of thymic occult cancer cells is during chemotherapy. Methods: With melanoma inoculated and genotoxic doxorubicin (Doxo) treated mouse model, we determined that the thymus, particularly the atrophied thymus, was able to harbor blood stream-circulating melanoma cells. Using specific in vivo + in vitro technique, where thymuses of doxorubicin- or PBS-treated mice are co-cultured with doxorubicin-treated melanoma cells in trans-well system we want to provide the insight of the changes in the status of cancer cells. Results: We found that chemotherapy-resulted DNA-damage response triggered p53 activation in non-malignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. Co-culture of PBS- or Doxo- treated thymus with Doxo-treated melanoma cells provides evidence that chemotherapy-altered inflammatory thymic microenvironment protects cancer cells from apoptosis via induction of dormancy. Conclusion: Therefore, the thymus, which becomes a pre-metastatic reservoir for non-lymphoid solid tumor cells under chemotherapy, should be a novel target in antitumor therapy for considering and preventing from tumor metastatic relapse. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/27984 | |
| dc.language.iso | en | |
| dc.provenance.legacyDownloads | 0 | |
| dc.title | Atrophied thymus can serve as a tumor reservoir for harboring melanoma cells | |
| dc.type | oral | |
| dc.type.material | text |