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Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.

Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW - Br. J. Cancer (2006)

Bottom Line: Here we show that arachidonic acid at concentrations <or=5 microM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely.This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398.These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

View Article: PubMed Central - PubMed

Affiliation: ProMPT Genito Urinary Cancer Research Group, Cancer Research UK. mbrown@picr.man.ac.uk

ABSTRACT
Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations

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PC-3 cells localise to adipocytes in BMS co-culture and take up lipids. 5 × 102 PC-3 cells co-cultured with primary long-term human BMS, visualised by staining with anti pan-cytokeratin and developed by DAB (brown). Bone marrow adipocytes and lipid droplets were visualised by staining with 0.5% Oil Red O. Images were captured utilising a Zeiss AxioVert 35 M with a C-Aprochromat × 63 1.2 NA water immersion objective lens. (A–C) Brightfield photomicrographs of PC-3 cells co-cultured with BMS showing PC-3 localisation to bone marrow adipocytes and lipid uptake. (D) Deconvolved brightfield image showing localisation of lipid droplets within the PC-3 cytoplasm. x and y panels show orthogonal planes of data along the white cross hair. (E–F) Brightfield photomicrograph of PC-3 cells co-cultured with primary human prostate fibroblasts.
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fig2: PC-3 cells localise to adipocytes in BMS co-culture and take up lipids. 5 × 102 PC-3 cells co-cultured with primary long-term human BMS, visualised by staining with anti pan-cytokeratin and developed by DAB (brown). Bone marrow adipocytes and lipid droplets were visualised by staining with 0.5% Oil Red O. Images were captured utilising a Zeiss AxioVert 35 M with a C-Aprochromat × 63 1.2 NA water immersion objective lens. (A–C) Brightfield photomicrographs of PC-3 cells co-cultured with BMS showing PC-3 localisation to bone marrow adipocytes and lipid uptake. (D) Deconvolved brightfield image showing localisation of lipid droplets within the PC-3 cytoplasm. x and y panels show orthogonal planes of data along the white cross hair. (E–F) Brightfield photomicrograph of PC-3 cells co-cultured with primary human prostate fibroblasts.

Mentions: We therefore hypothesised that malignant PECs may migrate towards adipocytes and utilise the lipids that they contained. To test this hypothesis, the PEC line PC-3 was seeded on to confluent long-term human BMS (Figure 2A–D) or primary prostate stroma (Figure 2E and F). PC-3 cells and lipid droplets were then visualised by staining with anti pan-cytokeratin, developed with DAB, and Oil Red O, respectively. Figure 2A and B illustrates that PC-3 cells migrate towards and form colonies around lipid-rich areas. High-resolution brightfield microscopy of PC-3 cells surrounding/in close proximity to lipid droplets shows that PC-3 cells take up lipids from the surrounding area of BMS (Figure 2C and D). This observation was confirmed using brightfield volumetric analysis of the PC-3/BMS co-culture. Figure 2D shows a de-convolved image of a PC-3 cell dual stained with anti pan-cytokeratin and Oil Red O with Z plane data collected at 0.2 μM steps. Along both the x and y axis are orthogonal planes of data bisecting a lipid droplet, confirming its location within the PC-3 cell.


Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.

Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW - Br. J. Cancer (2006)

PC-3 cells localise to adipocytes in BMS co-culture and take up lipids. 5 × 102 PC-3 cells co-cultured with primary long-term human BMS, visualised by staining with anti pan-cytokeratin and developed by DAB (brown). Bone marrow adipocytes and lipid droplets were visualised by staining with 0.5% Oil Red O. Images were captured utilising a Zeiss AxioVert 35 M with a C-Aprochromat × 63 1.2 NA water immersion objective lens. (A–C) Brightfield photomicrographs of PC-3 cells co-cultured with BMS showing PC-3 localisation to bone marrow adipocytes and lipid uptake. (D) Deconvolved brightfield image showing localisation of lipid droplets within the PC-3 cytoplasm. x and y panels show orthogonal planes of data along the white cross hair. (E–F) Brightfield photomicrograph of PC-3 cells co-cultured with primary human prostate fibroblasts.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2361380&req=5

fig2: PC-3 cells localise to adipocytes in BMS co-culture and take up lipids. 5 × 102 PC-3 cells co-cultured with primary long-term human BMS, visualised by staining with anti pan-cytokeratin and developed by DAB (brown). Bone marrow adipocytes and lipid droplets were visualised by staining with 0.5% Oil Red O. Images were captured utilising a Zeiss AxioVert 35 M with a C-Aprochromat × 63 1.2 NA water immersion objective lens. (A–C) Brightfield photomicrographs of PC-3 cells co-cultured with BMS showing PC-3 localisation to bone marrow adipocytes and lipid uptake. (D) Deconvolved brightfield image showing localisation of lipid droplets within the PC-3 cytoplasm. x and y panels show orthogonal planes of data along the white cross hair. (E–F) Brightfield photomicrograph of PC-3 cells co-cultured with primary human prostate fibroblasts.
Mentions: We therefore hypothesised that malignant PECs may migrate towards adipocytes and utilise the lipids that they contained. To test this hypothesis, the PEC line PC-3 was seeded on to confluent long-term human BMS (Figure 2A–D) or primary prostate stroma (Figure 2E and F). PC-3 cells and lipid droplets were then visualised by staining with anti pan-cytokeratin, developed with DAB, and Oil Red O, respectively. Figure 2A and B illustrates that PC-3 cells migrate towards and form colonies around lipid-rich areas. High-resolution brightfield microscopy of PC-3 cells surrounding/in close proximity to lipid droplets shows that PC-3 cells take up lipids from the surrounding area of BMS (Figure 2C and D). This observation was confirmed using brightfield volumetric analysis of the PC-3/BMS co-culture. Figure 2D shows a de-convolved image of a PC-3 cell dual stained with anti pan-cytokeratin and Oil Red O with Z plane data collected at 0.2 μM steps. Along both the x and y axis are orthogonal planes of data bisecting a lipid droplet, confirming its location within the PC-3 cell.

Bottom Line: Here we show that arachidonic acid at concentrations <or=5 microM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely.This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398.These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

View Article: PubMed Central - PubMed

Affiliation: ProMPT Genito Urinary Cancer Research Group, Cancer Research UK. mbrown@picr.man.ac.uk

ABSTRACT
Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations

Show MeSH
Related in: MedlinePlus