Thymic stromal lymphopoietin (TSLP) inhibits human colon tumor growth by promoting apoptosis of tumor cells
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Wenjie Yue1,2,*, Yuli Lin1,*, Xuguang Yang1, Bingji Li1, Jie Liu1,2, Rui He1,3
1Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai, 200032, People’s Republic of China
2Department of Digestive Diseases, Huashan Hospital, Shanghai, 200032, People’s Republic of China
3Biotherapy Research Center, Fudan University, Shanghai, 200032, People’s Republic of China
*These authors have contributed equally to this work
Rui He, e-mail: firstname.lastname@example.org
Jie Liu, e-mail: email@example.com
Keywords: TSLP, colon cancer, apoptosis, TSLPR, caspase3
Received: September 16, 2015 Accepted: February 06, 2016 Published: February 23, 2016
Thymic stromal lymphopoietin (TSLP) has recently been suggested in several epithelial cancers, either pro-tumor or anti-tumor. However, the role of TSLP in colon cancer remains unknown. We here found significantly decreased TSLP levels in tumor tissues compared with tumor-surrounding tissues of patients with colon cancer and TSLP levels negatively correlated with the clinical staging score of colon cancer. TSLPR, the receptor of TSLP, was expressed in all three colon cancer cell lines investigated and colon tumor tissues. The addition of TSLP significantly enhanced apoptosis of colon cancer cells in a TSLPR-dependent manner. Interestingly, TSLP selectively induced the apoptosis of colon cancer cells, but not normal colonic epithelial cells. Furthermore, we demonstrated that TSLP induced JNK and p38 activation and initiated apoptosis mainly through the extrinsic pathway, as caspase-8 inhibitor significantly reversed the apoptosis-promoting effect of TSLP. Finally, using a xenograft mouse model, we demonstrated that peritumoral administration of TSLP greatly reduced tumor growth accompanied with extensive tumor apoptotic response, which was abolished by tumor cell-specific knockdown of TSLPR. Collectively, our study reveals a novel anti-tumor effect of TSLP via direct promotion of the apoptosis of colon cancer cells, and suggests that TSLP could be of value in treating colon cancer.
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