title: Tie-2 regulates the stemness and metastatic properties of prostate cancer cells.
abstract: Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Kai-Dun
authors.initials: KD
authors.lastname: Tang
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Boris M
authors.initials: BM
authors.lastname: Holzapfel
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Terence Kin-Wah
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ma
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Jovanovic
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: An
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Clements
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland and Institute of Health and Biomedical Innovation, Queensland University of Technology and Translational Research Institute, Woolloongabba, QLD, Australia.
authors.forename: Ming-Tat
authors.initials: MT
authors.lastname: Ling
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042787:Receptor, TIE-2
keywords: Tie-2; cancer stem cells; metastasis; prostate cancer