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Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model.

Banyard J, Chung I, Wilson AM, Vetter G, Le Béchec A, Bielenberg DR, Zetter BR - Sci Rep (2013)

Bottom Line: DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin.Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering.We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family.

View Article: PubMed Central - PubMed

Affiliation: 1] Vascular Biology Program, Boston Children's Hospital, Karp Family Research Laboratories, 300 Longwood Ave., Boston, MA 02115 [2] Department of Surgery, Harvard Medical School, Boston, MA 02115.

ABSTRACT
Using an in vivo cycling strategy, we selected metastatic cancer cells from the lymph nodes (LN) of mice bearing orthotopic DU145 human prostate tumors. Repeated rounds of metastatic selection (LN1-LN4) progressively increased the epithelial phenotype, resulting in a new model of tumor cell mesenchymal-epithelial transition (MET). DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin. The MET in DU145-LN4 cells was accompanied by increased expression of the miR-200 family, and antimiRs to miR-200c and miR-141 induced an EMT. MET also correlated with the loss of miR-424. Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering. Our model provides evidence for spontaneous MET in vivo. We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family.

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Heat map profile of miRNA expression in the DU145-LN cell line model.RNA collected from DU145, DU145-LN1, DU145-LN2 and DU145-LN4 was analyzed using a miRCURY LNA array (Exiqon). Hierarchical clustering and heat map representation of miRNAs and cell lines. Global color scale shows maximum (red) and minimum (blue) miRNA expression level.
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f4: Heat map profile of miRNA expression in the DU145-LN cell line model.RNA collected from DU145, DU145-LN1, DU145-LN2 and DU145-LN4 was analyzed using a miRCURY LNA array (Exiqon). Hierarchical clustering and heat map representation of miRNAs and cell lines. Global color scale shows maximum (red) and minimum (blue) miRNA expression level.

Mentions: The MET-like program in these cells suggested a mechanism of coordinated gene expression changes. We examined the miRNA profile in these cells using miRNA gene chips and discovered that several miRNAs showed a pattern of progressively increased or decreased expression across the metastatic DU145 cell line model. The most significantly increased miRNAs in the microarray were those of the miRNA-200 family (miR200a, miR200b, miR200c and miR-141). The miR-200 family also includes miR-429, which also showed some increased expression in the DU145-LN cell microarray, but did not reach the threshold filter for further analysis. The most significantly decreased miRNA was miR-424 (Figure 4). MiR-200c was the most changed miRNA in the DU145-LN4 microarray data, with 5.5 fold increase in expression relative to parental DU145, miR-141 was the second most changed (4.6 fold), followed by miR-200b (3.2 fold) and miR-200a (2.6 fold).


Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model.

Banyard J, Chung I, Wilson AM, Vetter G, Le Béchec A, Bielenberg DR, Zetter BR - Sci Rep (2013)

Heat map profile of miRNA expression in the DU145-LN cell line model.RNA collected from DU145, DU145-LN1, DU145-LN2 and DU145-LN4 was analyzed using a miRCURY LNA array (Exiqon). Hierarchical clustering and heat map representation of miRNAs and cell lines. Global color scale shows maximum (red) and minimum (blue) miRNA expression level.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818652&req=5

f4: Heat map profile of miRNA expression in the DU145-LN cell line model.RNA collected from DU145, DU145-LN1, DU145-LN2 and DU145-LN4 was analyzed using a miRCURY LNA array (Exiqon). Hierarchical clustering and heat map representation of miRNAs and cell lines. Global color scale shows maximum (red) and minimum (blue) miRNA expression level.
Mentions: The MET-like program in these cells suggested a mechanism of coordinated gene expression changes. We examined the miRNA profile in these cells using miRNA gene chips and discovered that several miRNAs showed a pattern of progressively increased or decreased expression across the metastatic DU145 cell line model. The most significantly increased miRNAs in the microarray were those of the miRNA-200 family (miR200a, miR200b, miR200c and miR-141). The miR-200 family also includes miR-429, which also showed some increased expression in the DU145-LN cell microarray, but did not reach the threshold filter for further analysis. The most significantly decreased miRNA was miR-424 (Figure 4). MiR-200c was the most changed miRNA in the DU145-LN4 microarray data, with 5.5 fold increase in expression relative to parental DU145, miR-141 was the second most changed (4.6 fold), followed by miR-200b (3.2 fold) and miR-200a (2.6 fold).

Bottom Line: DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin.Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering.We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family.

View Article: PubMed Central - PubMed

Affiliation: 1] Vascular Biology Program, Boston Children's Hospital, Karp Family Research Laboratories, 300 Longwood Ave., Boston, MA 02115 [2] Department of Surgery, Harvard Medical School, Boston, MA 02115.

ABSTRACT
Using an in vivo cycling strategy, we selected metastatic cancer cells from the lymph nodes (LN) of mice bearing orthotopic DU145 human prostate tumors. Repeated rounds of metastatic selection (LN1-LN4) progressively increased the epithelial phenotype, resulting in a new model of tumor cell mesenchymal-epithelial transition (MET). DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin. The MET in DU145-LN4 cells was accompanied by increased expression of the miR-200 family, and antimiRs to miR-200c and miR-141 induced an EMT. MET also correlated with the loss of miR-424. Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering. Our model provides evidence for spontaneous MET in vivo. We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family.

Show MeSH
Related in: MedlinePlus