1. Thymic stromal lymphopoietin is a key mediator of breast cancer progression.
- Author
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Olkhanud PB, Rochman Y, Bodogai M, Malchinkhuu E, Wejksza K, Xu M, Gress RE, Hesdorffer C, Leonard WJ, and Biragyn A
- Subjects
- Animals, Breast Neoplasms pathology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Cytokines genetics, Disease Progression, Female, Humans, Inflammation immunology, Inflammation metabolism, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-13 immunology, Interleukin-13 metabolism, Lung Neoplasms secondary, Mammary Neoplasms, Animal metabolism, Mammary Neoplasms, Animal pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, RNA Interference, RNA, Small Interfering, Th2 Cells immunology, Tumor Escape, Thymic Stromal Lymphopoietin, Breast Neoplasms immunology, Cytokines metabolism, Mammary Neoplasms, Animal immunology
- Abstract
Inflammation is a double-edged sword that can promote or suppress cancer progression. In this study, we report that thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs, is also expressed in human and murine cancers. Our studies with murine cancer cells indicate that TSLP plays an essential role in cancer escape, as its inactivation in cancer cells alone was sufficient to almost completely abrogate cancer progression and lung metastasis. The cancer-promoting activity of TSLP primarily required signaling through the TSLP receptor on CD4(+) T cells, promoting Th2-skewed immune responses and production of immunosuppressive factors such as IL-10 and IL-13. Expression of TSLP therefore may be a useful prognostic marker, and its targeting could have therapeutic potential.
- Published
- 2011
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