title: Cells susceptible to epithelial-mesenchymal transition are enriched in stem-like side population cells from prostate cancer.
abstract: Accumulating evidence suggests that epithelial-mesenchymal transition (EMT) acts as an important factor for the promotion of tumor progression. Strategies for suppressing EMT remain the subject of ongoing research. In the present study, fluorescence-activated cell sorting (FACS) was used to isolate side population (SP) cells from human prostate cancer (PCa) cell lines and xenograft tissues. After identifying their molecular and functional stem-like characteristics, stem-like SP cells from a cell line and from xenograft tissue were transfected with hypoxia inducible factor-1α (HIF-1α). The potential of the prostate stem-like SP cells to undergo EMT was compared with that in their bulk counterparts after HIF-1α introduction. Stem-like SP cells acquired more complete EMT molecular features and exhibited stronger aggressive capability than the homologous bulk population cells both in vitro (proliferation and invasion) and in vivo (tumorigenesis and metastasis formation). We, therefore, concluded that EMT is closely associated with tumor heterogeneity, and that PCa cells susceptible to EMT are enriched in stem-like SP cells. These findings disclose a new approach, targeting the cellular basis of the EMT process that may help to identify effective and accurate methods for suppressing tumor growth and preventing distant dissemination.
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yong
authors: Y
authors: Luo
authors: Department of Urology, Beijing Shijingshan Hospital, Beijing 100043, P.R. China.
authors: Xinhao
authors: X
authors: Cui
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Jiahui
authors: J
authors: Zhao
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yili
authors: Y
authors: Han
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Mingchuan
authors: M
authors: Li
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yunhua
authors: Y
authors: Lin
authors: Department of Urology, Beijing Anzhen Hospital, Affiliated to Capital Medical University, Beijing 100029, P.R. China.
authors: Yongguang
authors: Y
authors: Jiang
authors: Department of Endocrinology, Beijing Jishuitan Hospital, The 4th Clinical Medical College of Peking University, Beijing 100035, P.R. China.
authors: Ling
authors: L
authors: Lan
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001859:Bone Neoplasms / Q000556:secondary; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D058985:Side-Population Cells / Q000166:cytology / Q000473:pathology*; D014162:Transfection; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014746:Vimentin; D051176:beta Catenin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2