Atrophied thymus, a tumor reservoir for harboring melanoma cells

Olga Sizova, Denis Kuriatnikov, Ying Liu, Dong Ming Su

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Tumor metastatic relapse is the primary cause for cancerassociated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, a central T-cell immune organ, has been suggested to be a premetastatic tumor reservoir for Blymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell-inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor blood stream-circulating melanoma cells. In addition, a chemotherapy- induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemoresistant state.

Original languageEnglish
Pages (from-to)1652-1664
Number of pages13
JournalMolecular Cancer Research
Volume16
Issue number11
DOIs
StatePublished - 1 Nov 2018

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Thymus Neoplasms
Melanoma
Thymus Gland
Neoplasms
Drug Therapy
Recurrence
Cell Aging
Thymocytes
Radio
Doxorubicin
DNA Damage
Epithelial Cells
T-Lymphocytes

Cite this

Sizova, Olga ; Kuriatnikov, Denis ; Liu, Ying ; Su, Dong Ming. / Atrophied thymus, a tumor reservoir for harboring melanoma cells. In: Molecular Cancer Research. 2018 ; Vol. 16, No. 11. pp. 1652-1664.
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abstract = "Tumor metastatic relapse is the primary cause for cancerassociated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, a central T-cell immune organ, has been suggested to be a premetastatic tumor reservoir for Blymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell-inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor blood stream-circulating melanoma cells. In addition, a chemotherapy- induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemoresistant state.",
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Atrophied thymus, a tumor reservoir for harboring melanoma cells. / Sizova, Olga; Kuriatnikov, Denis; Liu, Ying; Su, Dong Ming.

In: Molecular Cancer Research, Vol. 16, No. 11, 01.11.2018, p. 1652-1664.

Research output: Contribution to journalArticleResearchpeer-review

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