RT Journal Article
SR Electronic
T1 Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 692
OP 702
DO 10.1136/jclinpath-2015-203001
VO 68
IS 9
A1 Gallagher, Michael F
A1 Salley, Yvonne
A1 Spillane, Cathy D
A1 Ffrench, Brendan
A1 El Baruni, Salah
A1 Blacksheilds, Gordon
A1 Smyth, Paul
A1 Martin, Cara
A1 Sheils, Orla
A1 Watson, William
A1 O'Leary, John J
YR 2015
UL http://jcp.bmj.com/content/68/9/692.abstract
AB 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.