A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer

Figure S5 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

H3K9me3 levels increase upon treatment with QC6352. Changes in H3K9me3 levels are depicted according to genomic location.</p

Supplementary Figure Legends from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

This file contains the legends to all Supplementary Figures</p

Figure S2 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

KDM4B, C, or D do not control proliferation and xenograft tumor growth of BCSC1.</p

Figure S3 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

QC6352 strongly decreases proliferation and sphere formation of a second breast cancer stem cell line (BCSC2). Other breast cancer-targeting agents like QC6688 and paclitaxel are unable to abolish secondary sphere formation in BCSC1 or BCSC2.</p

Figure S4 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

Additional evidence showing control of EGFR expression by QC6352 is presented here. The specific EGFR inhibitor erlotinib diminishes proliferation and sphere formation in BCSC1 and BCSC2.</p

Figure S6 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

Treatment with QC6352 inhibits xenograft tumor growth of a second breast cancer stem cell line (BCSC2).</p

Figure S1 from KDM4 Inhibition Targets Breast Cancer Stem–like Cells

Characterization of the breast cancer stem cell line BCSC2 in vitro and in vivo. Like BCSC1 in Figure 1, BCSC2-derived xenografts also recapitulate the original patient tumor.</p