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Saturated and mono-unsaturated lysophosphatidylcholine metabolism in tumour cells: a potential therapeutic target for preventing metastases.

Raynor A, Jantscheff P, Ross T, Schlesinger M, Wilde M, Haasis S, Dreckmann T, Bendas G, Massing U - Lipids Health Dis (2015)

Bottom Line: According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice.Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.These data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided.

View Article: PubMed Central - PubMed

Affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. raynor@tumorbio.uni-freiburg.de.

ABSTRACT

Background: Metastasis is the leading cause of mortality in malignant diseases. Patients with metastasis often show reduced Lysophosphatidylcholine (LysoPC) plasma levels and treatment of metastatic tumour cells with saturated LysoPC species reduced their metastatic potential in vivo in mouse experiments. To provide a first insight into the interplay of tumour cells and LysoPC, the interactions of ten solid epithelial tumour cell lines and six leukaemic cell lines with saturated and mono-unsaturated LysoPC species were explored.

Methods: LysoPC metabolism by the different tumour cells was investigated by a combination of cell culture assays, GC and MS techniques. Functional consequences of changed membrane properties were followed microscopically by detecting lateral lipid diffusion or cellular migration. Experimental metastasis studies in mice were performed after pretreatment of B16.F10 melanoma cells with LysoPC and FFA, respectively.

Results: In contrast to the leukaemic cells, all solid tumour cells show a very fast extracellular degradation of the LysoPC species to free fatty acids (FFA) and glycerophosphocholine. We provide evidence that the formerly LysoPC bound FFA were rapidly incorporated into the cellular phospholipids, thereby changing the FA-compositions accordingly. A massive increase of the neutral lipid amount was observed, inducing the formation of lipid droplets. Saturated LysoPC and to a lesser extent also mono-unsaturated LysoPC increased the cell membrane rigidity, which is assumed to alter cellular functions involved in metastasis. According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice. Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.

Conclusion: These data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided. In contrast to the physiological mix of LysoPC species, saturated and mono-unsaturated LysoPC alone apparently attenuate the metastatic activity of tumours and the artificial increase of saturated and mono-unsaturated LysoPC in plasma appears as novel therapeutic approach to interfere with metastasis.

No MeSH data available.


Related in: MedlinePlus

LysoPC plasma level in healthy mice and tumour bearing mice. Total LysoPC plasma levels of healthy mice (n = 4) and mice intravenously injected with B16.F10 melanoma cells; one (n = 3), two (n = 3) and three (n = 3) weeks after injection of tumour cells. LysoPC levels were determined by HPLC MS/MS analysis. Values compared by ANOVA: * p ≤ 0.05, ** p ≤ 0.01
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Fig6: LysoPC plasma level in healthy mice and tumour bearing mice. Total LysoPC plasma levels of healthy mice (n = 4) and mice intravenously injected with B16.F10 melanoma cells; one (n = 3), two (n = 3) and three (n = 3) weeks after injection of tumour cells. LysoPC levels were determined by HPLC MS/MS analysis. Values compared by ANOVA: * p ≤ 0.05, ** p ≤ 0.01

Mentions: Compared to healthy mice, LysoPC plasma levels in mice were significantly reduced two or three weeks after injection of B16.F10 melanoma cells while this difference was not yet detectable already one week after injection of the tumour cells. No differences were found between healthy mice and tumour bearing mice one week after tumour cell injection (Fig. 6). With regard to the different LysoPC species, the most pronounced decrease was found for LysoPC 16:0. There was also an apparent decrease in LysoPC 18:2 and LysoPC 20:4; however these differences were not significant.Fig. 6


Saturated and mono-unsaturated lysophosphatidylcholine metabolism in tumour cells: a potential therapeutic target for preventing metastases.

Raynor A, Jantscheff P, Ross T, Schlesinger M, Wilde M, Haasis S, Dreckmann T, Bendas G, Massing U - Lipids Health Dis (2015)

LysoPC plasma level in healthy mice and tumour bearing mice. Total LysoPC plasma levels of healthy mice (n = 4) and mice intravenously injected with B16.F10 melanoma cells; one (n = 3), two (n = 3) and three (n = 3) weeks after injection of tumour cells. LysoPC levels were determined by HPLC MS/MS analysis. Values compared by ANOVA: * p ≤ 0.05, ** p ≤ 0.01
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4499168&req=5

Fig6: LysoPC plasma level in healthy mice and tumour bearing mice. Total LysoPC plasma levels of healthy mice (n = 4) and mice intravenously injected with B16.F10 melanoma cells; one (n = 3), two (n = 3) and three (n = 3) weeks after injection of tumour cells. LysoPC levels were determined by HPLC MS/MS analysis. Values compared by ANOVA: * p ≤ 0.05, ** p ≤ 0.01
Mentions: Compared to healthy mice, LysoPC plasma levels in mice were significantly reduced two or three weeks after injection of B16.F10 melanoma cells while this difference was not yet detectable already one week after injection of the tumour cells. No differences were found between healthy mice and tumour bearing mice one week after tumour cell injection (Fig. 6). With regard to the different LysoPC species, the most pronounced decrease was found for LysoPC 16:0. There was also an apparent decrease in LysoPC 18:2 and LysoPC 20:4; however these differences were not significant.Fig. 6

Bottom Line: According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice.Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.These data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided.

View Article: PubMed Central - PubMed

Affiliation: Department of Lipids & Liposomes, Tumor Biology Center, Clinical Research, Breisacher Str. 117, 79106, Freiburg, Germany. raynor@tumorbio.uni-freiburg.de.

ABSTRACT

Background: Metastasis is the leading cause of mortality in malignant diseases. Patients with metastasis often show reduced Lysophosphatidylcholine (LysoPC) plasma levels and treatment of metastatic tumour cells with saturated LysoPC species reduced their metastatic potential in vivo in mouse experiments. To provide a first insight into the interplay of tumour cells and LysoPC, the interactions of ten solid epithelial tumour cell lines and six leukaemic cell lines with saturated and mono-unsaturated LysoPC species were explored.

Methods: LysoPC metabolism by the different tumour cells was investigated by a combination of cell culture assays, GC and MS techniques. Functional consequences of changed membrane properties were followed microscopically by detecting lateral lipid diffusion or cellular migration. Experimental metastasis studies in mice were performed after pretreatment of B16.F10 melanoma cells with LysoPC and FFA, respectively.

Results: In contrast to the leukaemic cells, all solid tumour cells show a very fast extracellular degradation of the LysoPC species to free fatty acids (FFA) and glycerophosphocholine. We provide evidence that the formerly LysoPC bound FFA were rapidly incorporated into the cellular phospholipids, thereby changing the FA-compositions accordingly. A massive increase of the neutral lipid amount was observed, inducing the formation of lipid droplets. Saturated LysoPC and to a lesser extent also mono-unsaturated LysoPC increased the cell membrane rigidity, which is assumed to alter cellular functions involved in metastasis. According to that, saturated and mono-unsaturated LysoPC as well as the respective FFA reduced the metastatic potential of B16.F10 cells in mice. Application of high doses of liposomes mainly consisting of saturated PC was shown to be a suitable way to strongly increase the plasma level of saturated LysoPC in mice.

Conclusion: These data show that solid tumours display a high activity to hydrolyse LysoPC followed by a very rapid uptake of the resulting FFA; a mechanistic model is provided. In contrast to the physiological mix of LysoPC species, saturated and mono-unsaturated LysoPC alone apparently attenuate the metastatic activity of tumours and the artificial increase of saturated and mono-unsaturated LysoPC in plasma appears as novel therapeutic approach to interfere with metastasis.

No MeSH data available.


Related in: MedlinePlus