title: Thymic stromal lymphopoietin (TSLP) inhibits human colon tumor growth by promoting apoptosis of tumor cells.
abstract: 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.
authors.affiliation: Department 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.|Department of Digestive Diseases, Huashan Hospital, Shanghai, 200032, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yue
authors.affiliation: Department 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.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department 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.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department 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.
authors.forename: Bingji
authors.initials: B
authors.lastname: Li
authors.affiliation: Department 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.|Department of Digestive Diseases, Huashan Hospital, Shanghai, 200032, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department 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.|Biotherapy Research Center, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: He
mesh_terms: D000236:Adenoma / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018121:Receptors, Cytokine / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D016207:Cytokines; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin
keywords: TSLP; TSLPR; apoptosis; caspase3; colon cancer