Disruption of the thymic microenvironment is associated with thymic involution of transitional cell cancer.
BACKGROUND
During bladder tumorigenesis, thymopoiesis is usually downregulated. Considering that the thymus is the site of most T-cell development, this phenomenon may be related to thymic involution. However, the mechanisms involved in this phenomenon remain to be elucidated.


METHODS
An MB 49 murine bladder tumor model was used to identify mechanisms that might underlie this process.


RESULTS
The thymuses of tumor-bearing mice showed less cellularity than those of healthy mice. Involution was found to be associated with less proliferation and more apoptosis of thymic epithelial cells (TEC). Foxn1, KGF, and IL-7, three factors known to be involved in thymic development, were also downregulated in the thymuses of tumor bearers. When these mice were intravenously injected with KGF, the thymic microenvironment, thymopoiesis, and T-cell differentiation all returned to near normal status.


CONCLUSIONS
The decreases in thymopoiesis and impaired T-cell differentiation may be attributable to changes in the thymic microenvironment. Improving the function of TEC, rather than T-cell progenitors, should be the focus of therapy.
Research Center, The Shengjing Hospital, China Medical University, Shenyang, PR China.
Yan
Y
Song
Ruoxing
R
Yu
Changshan
C
Wang
Feng
F
Chi
Zhibin
Z
Guo
Xike
X
Zhu
D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
C496453:FGF7 protein, human; D051858:Forkhead Transcription Factors; C508605:IL7 protein, human; D015851:Interleukin-7; C090140:Whn protein; D051523:Fibroblast Growth Factor 7