title: Angiopoietin-like protein 2 induces androgen-independent and malignant behavior in human prostate cancer cells.
abstract: Angiopoietin-like proteins (ANGPTLs), which comprise 7 members (ANGPTL1-ANGPTL7), structurally resemble angiopoietins. We investigated the roles of ANGPTLs in the acquisition of androgen independence and the malignant behavior of human prostate cancer cells. Expression of ANGPTL messenger RNA (mRNA) and proteins were ascertained using RT-qPCR and western blot analysis in human prostate cancer cell lines. Androgen‑dependent LNCaP and androgen-independent LNCaP/AI cells, respectively, were cultured in fetal bovine and charcoal-stripped medium. Cell proliferation, androgen dependence, migration and invasion, respectively, were examined under the overexpression and knockdown of ANGPTL2 by transfection of ANGPTL2 cDNA and its small‑interfering RNA (siRNA). The effects of exogenous ANGPTL2 and blocking of its receptor, integrin α5β1, were also investigated. Human prostate cancer cell lines predominantly expressed ANGPTL2 among the members. Interrupting ANGPTL2 expression with siRNA suppressed the proliferation, migration and invasion of LNCaP cells. LNCaP/AI cells showed a higher ANGPTL2 expression than that of LNCaP cells. Furthermore, siRNA led to apoptosis of LNCaP/AI cells. The ANGPTL2-overexpressing LNCaP cells markedly increased proliferation, epithelial-to-mesenchymal transition (EMT) and malignant behavior in androgen‑deprived medium. The migration rates were increased depending on the concentration of ANGPTL2 recombinant protein and were inhibited by anti-integrin α5β1 antibodies. To the best of our knowledge, this is the first study to elucidate the expression of ANGPTL2 in human prostate cancer cells. ANGPTL2 may be important in the acquisition of androgen independency and tumor progression of prostate cancer in an autocrine and/or paracrine manner via the integrin α5β1 receptor. Targeting ANGPTL2 may therefore be an efficacious therapeutic modality for prostate cancer.
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Sato
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Mutsushi
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Hasama, Yufu-city, Oita 879-5593, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
mesh_terms: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D051017:Apoptosis Regulatory Proteins; D039081:Integrin alpha5beta1