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Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells.

Josson S, Sharp S, Sung SY, Johnstone PA, Aneja R, Wang R, Gururajan M, Turner T, Chung LW, Yates C - J Oncol (2010)

Bottom Line: Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells.However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells.Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Emory School of Medicine, Atlanta, GA 30311, USA.

ABSTRACT
HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model. Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaP(E) cells compared to ARCaP(M) cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation.

No MeSH data available.


Related in: MedlinePlus

Effect of Anti-alpha v integrin (CNT095) on tumor-stroma interactions. ARCaPM and ARCaPE, cells were pretreated with CNT095 antibody was cocultured with HS-27a stromal cells for 24 hours, and radiated with 4 Gy. Cell colony forming capacity was assayed using clonogenic assay. ARCaPM data are normalized to ARCaPM   control levels, and ARCaPE data are normalized to ARCaPE   control levels.
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fig5: Effect of Anti-alpha v integrin (CNT095) on tumor-stroma interactions. ARCaPM and ARCaPE, cells were pretreated with CNT095 antibody was cocultured with HS-27a stromal cells for 24 hours, and radiated with 4 Gy. Cell colony forming capacity was assayed using clonogenic assay. ARCaPM data are normalized to ARCaPM control levels, and ARCaPE data are normalized to ARCaPE control levels.

Mentions: To determine the influence of intergin alpha v cell adhesion with bone microenvironment, we performed similar clonogenic formation assay. Pretreatment with CNT095 antibody significantly decreased the clonogenic ability of both ARCaPM and ARCaPE cells in homotyic cultures (Figure 5, P < .001). Additionally, CNT095 significantly decreased bone stroma-induced radiation resistance in cancer cells in both ARCaPM  (P < .001) and ARCaPE  (P < .001) cancer cells, with the most significant reduction in cocultured conditions (P < .001) (Figure 5). Taken together, these results suggest that bone stroma-induced radiation resistance is mediated through both E-cadherin and integrin alpha v beta signaling in epithelial and mesenchymal cells. Thus, E-cadherin and integrin alpha v beta appear to present novel targets for metastatic and radiation resistant cells.


Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells.

Josson S, Sharp S, Sung SY, Johnstone PA, Aneja R, Wang R, Gururajan M, Turner T, Chung LW, Yates C - J Oncol (2010)

Effect of Anti-alpha v integrin (CNT095) on tumor-stroma interactions. ARCaPM and ARCaPE, cells were pretreated with CNT095 antibody was cocultured with HS-27a stromal cells for 24 hours, and radiated with 4 Gy. Cell colony forming capacity was assayed using clonogenic assay. ARCaPM data are normalized to ARCaPM   control levels, and ARCaPE data are normalized to ARCaPE   control levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2926670&req=5

fig5: Effect of Anti-alpha v integrin (CNT095) on tumor-stroma interactions. ARCaPM and ARCaPE, cells were pretreated with CNT095 antibody was cocultured with HS-27a stromal cells for 24 hours, and radiated with 4 Gy. Cell colony forming capacity was assayed using clonogenic assay. ARCaPM data are normalized to ARCaPM control levels, and ARCaPE data are normalized to ARCaPE control levels.
Mentions: To determine the influence of intergin alpha v cell adhesion with bone microenvironment, we performed similar clonogenic formation assay. Pretreatment with CNT095 antibody significantly decreased the clonogenic ability of both ARCaPM and ARCaPE cells in homotyic cultures (Figure 5, P < .001). Additionally, CNT095 significantly decreased bone stroma-induced radiation resistance in cancer cells in both ARCaPM  (P < .001) and ARCaPE  (P < .001) cancer cells, with the most significant reduction in cocultured conditions (P < .001) (Figure 5). Taken together, these results suggest that bone stroma-induced radiation resistance is mediated through both E-cadherin and integrin alpha v beta signaling in epithelial and mesenchymal cells. Thus, E-cadherin and integrin alpha v beta appear to present novel targets for metastatic and radiation resistant cells.

Bottom Line: Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells.However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells.Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Emory School of Medicine, Atlanta, GA 30311, USA.

ABSTRACT
HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model. Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaP(E) exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaP(E) cells compared to ARCaP(M) cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation.

No MeSH data available.


Related in: MedlinePlus