Atrophied thymus can serve as a tumor reservoir for harboring melanoma cells

Date

2018-03-14

Authors

Kuriatnikov, Denis
Sizova, Olga
Su, Dong-Ming

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0000-0003-3441-9064 (Sizova, Olga)

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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.

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Research Appreciation Day Award Winner - 2018 Quest Diagnostics, Quest Diagnostics 2018 Research Award

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