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M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues.

Puxbaum V, Nimmerfall E, Bäuerl C, Taub N, Blaas PM, Wieser J, Mikula M, Mikulits W, Ng KM, Yeoh GC, Mach L - J. Hepatol. (2012)

Bottom Line: Forced expression of M6P/IGF2R restores intracellular transport of cathepsins to lysosomes and concomitantly reduces the tumorigenicity and invasive potential of these cells.We also demonstrate that functional M6P-binding sites are important for the anti-invasive properties of M6P/IGF2R, whereas the capacity to bind IGF-II is dispensable for the anti-invasive activity of the receptor in liver cells.M6P/IGF2R restricts liver cell invasion by preventing the pericellular action of M6P-modified proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.

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Effects of transient M6P/IGF2R knock-down on MIM-1-4 cells. (A) Transfection of MIM-1–4 cells with siRNA oligonucleotides or transfection reagent alone (control). Membrane extracts (50 μg protein) were then immunoblotted with anti-M6P/IGF2R antibodies. LAMP-1 was used as loading control. (B) Transfected cells were incubated for 24 h prior to determination of β-N-acetylhexosaminidase (HEX) activity in cell lysates and media. The secretion levels are presented as means ± SD of 4 independent experiments. (C) Invasion assays using 10% FBS ± 10 ng/ml mouse HGF as chemoattractant. Data are presented as means ± SEM of 3–6 independent experiments.
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f0050: Effects of transient M6P/IGF2R knock-down on MIM-1-4 cells. (A) Transfection of MIM-1–4 cells with siRNA oligonucleotides or transfection reagent alone (control). Membrane extracts (50 μg protein) were then immunoblotted with anti-M6P/IGF2R antibodies. LAMP-1 was used as loading control. (B) Transfected cells were incubated for 24 h prior to determination of β-N-acetylhexosaminidase (HEX) activity in cell lysates and media. The secretion levels are presented as means ± SD of 4 independent experiments. (C) Invasion assays using 10% FBS ± 10 ng/ml mouse HGF as chemoattractant. Data are presented as means ± SEM of 3–6 independent experiments.


M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues.

Puxbaum V, Nimmerfall E, Bäuerl C, Taub N, Blaas PM, Wieser J, Mikula M, Mikulits W, Ng KM, Yeoh GC, Mach L - J. Hepatol. (2012)

Effects of transient M6P/IGF2R knock-down on MIM-1-4 cells. (A) Transfection of MIM-1–4 cells with siRNA oligonucleotides or transfection reagent alone (control). Membrane extracts (50 μg protein) were then immunoblotted with anti-M6P/IGF2R antibodies. LAMP-1 was used as loading control. (B) Transfected cells were incubated for 24 h prior to determination of β-N-acetylhexosaminidase (HEX) activity in cell lysates and media. The secretion levels are presented as means ± SD of 4 independent experiments. (C) Invasion assays using 10% FBS ± 10 ng/ml mouse HGF as chemoattractant. Data are presented as means ± SEM of 3–6 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3401376&req=5

f0050: Effects of transient M6P/IGF2R knock-down on MIM-1-4 cells. (A) Transfection of MIM-1–4 cells with siRNA oligonucleotides or transfection reagent alone (control). Membrane extracts (50 μg protein) were then immunoblotted with anti-M6P/IGF2R antibodies. LAMP-1 was used as loading control. (B) Transfected cells were incubated for 24 h prior to determination of β-N-acetylhexosaminidase (HEX) activity in cell lysates and media. The secretion levels are presented as means ± SD of 4 independent experiments. (C) Invasion assays using 10% FBS ± 10 ng/ml mouse HGF as chemoattractant. Data are presented as means ± SEM of 3–6 independent experiments.
Bottom Line: Forced expression of M6P/IGF2R restores intracellular transport of cathepsins to lysosomes and concomitantly reduces the tumorigenicity and invasive potential of these cells.We also demonstrate that functional M6P-binding sites are important for the anti-invasive properties of M6P/IGF2R, whereas the capacity to bind IGF-II is dispensable for the anti-invasive activity of the receptor in liver cells.M6P/IGF2R restricts liver cell invasion by preventing the pericellular action of M6P-modified proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.

Show MeSH
Related in: MedlinePlus