title: Interleukin-12 inhibits the survival of human colon cancer stem cells in vitro and their tumor initiating capacity in mice.
abstract: Interleukin-12 (IL-12) is a potent immunomodulatory cytokine with unknown direct effect on the property of cancer stem cells (CSCs). In this study, we investigated the capacity of IL-12 to regulate the self-renewal and differentiation of human colon CSCs in vitro, as well as the effect of IL-12 on the growth of tumors initiated by CSCs in mice. After over-expression of IL-12 with lentiviral transfection, CSCs exhibited reduced invasiveness and tumorsphere formation in association with increased apoptosis in vitro. After injection into NOD/SCID mice, tumors initiated by CSCs transfected with IL-12 showed markedly reduced rate of growth. Mechanistic studies revealed that over-expression of IL-12 reduced the expression of IL-4 and STAT6 in CSCs. Thus, our study demonstrates a potentially beneficial role of IL-12 in directly limiting the malignant phenotype of CSCs.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Yin
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Gan-feng
authors.initials: GF
authors.lastname: Xie
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Hou-jie
authors.initials: HJ
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D050800:STAT6 Transcription Factor; D018664:Interleukin-12; D015847:Interleukin-4