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Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones.
Gallagher, Michael F; Salley, Yvonne; Spillane, Cathy D; Ffrench, Brendan; El Baruni, Salah; Blacksheilds, Gordon; Smyth, Paul; Martin, Cara; Sheils, Orla; Watson, William; O'Leary, John J.
Afiliación
  • Gallagher MF; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • Salley Y; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • Spillane CD; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • Ffrench B; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • El Baruni S; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • Blacksheilds G; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland.
  • Smyth P; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland.
  • Martin C; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
  • Sheils O; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland.
  • Watson W; School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin 4, Ireland.
  • O'Leary JJ; Department of Histopathology, Central Pathology Laboratory, University of Dublin, Trinity College, St James Hospital, Dublin 8, Ireland Pathology Department, Coombe Women's and Infants University Hospital, Dublin 8, Ireland.
J Clin Pathol ; 68(9): 692-702, 2015 Sep.
Article en En | MEDLINE | ID: mdl-26038242
AIMS: Targeting the stem cell properties of tumor-initiating cells is an avenue through which cancer treatment may be improved. Before this can be achieved, so-called 'cancer stem cell' (CSC) models must be developed and characterized in specific malignancies. METHODS: In this study, holoclone formation assays were used to characterise stem-like molecular signatures in prostate cancer (PCa) cells. RESULTS: LNCaP and PC3 parent cells were capable of responding to stem cell differentiation morphogen retinoic acid (RA), suggesting the presence of inherent stem-like properties. LNCaP cells, which represent early, androgen-responsive disease, formed holoclones after twenty six days. PC3 cells, which represent advanced, metastatic, castration-resistant disease, formed holoclones after only six days. Holoclones displayed decreased expression of RA-genes, suggesting a more immature, less differentiated phenotype. Gene and microRNA arrays demonstrated that holoclones downregulated a number of stem cell differentiation regulators while displaying enhanced regulation of G2 to M transition and the mitotic spindle checkpoint components of the cell cycle. PC3 holoclones displayed pronounced downregulation of known regulators of osteoblast differentiation from mesenchymal stem cells and Epithelial Mesenchymal Transition. CONCLUSIONS: Our results suggest that some PCa cells retain the ability to transition to a more immature state in which differentiation and metastatic mechanisms are suppressed. The highlighting of osteoblast differentiation regulators in this mechanism is particularly notable, considering the propensity of PCa to metastasise to bone.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Neoplasias de la Próstata / Células Madre Neoplásicas / Diferenciación Celular / Transcriptoma Límite: Humans / Male Idioma: En Revista: J Clin Pathol Año: 2015 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Neoplasias de la Próstata / Células Madre Neoplásicas / Diferenciación Celular / Transcriptoma Límite: Humans / Male Idioma: En Revista: J Clin Pathol Año: 2015 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Reino Unido