TY - JOUR
T1 - Atrophied thymus, a tumor reservoir for harboring melanoma cells
AU - Sizova, Olga
AU - Kuriatnikov, Denis
AU - Liu, Ying
AU - Su, Dong Ming
N1 - Funding Information:
This work was partially supported by The American Association of Immunologists (AAI) Careers in Immunology Fellowship Program, awarded to O. Sizova.
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055912804&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-18-0308
DO - 10.1158/1541-7786.MCR-18-0308
M3 - Article
C2 - 30006356
AN - SCOPUS:85055912804
SN - 1541-7786
VL - 16
SP - 1652
EP - 1664
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 11
ER -