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Inhibition of glioma cell lysosome exocytosis inhibits glioma invasion.

Abstract
Cancer cells invade by secreting enzymes that degrade the extracellular matrix and these are sequestered in lysosomal vesicles. In this study, the effects of the selective lysosome lysing drug GPN and the lysosome exocytosis inhibitor vacuolin-1 on lysosome exocytosis were studied to determine their effect on glioma cell migration and invasion. Both GPN and vacuolin-1 evidently inhibited migration and invasion in transwell experiments and scratch experiments. There are more lysosomes located on the cell membrane of glioma cells than of astrocytes. GPN decreased the lysosome number on the cell membrane. We found that rab27A was expressed in glioma cells, and colocalized with cathepsin D in lysosome. RNAi-Rab27A inhibited lysosome cathepsin D exocytosis and glioma cell invasion in an in vitro assay. Inhibition of cathepsin D inhibited glioma cell migration. The data suggest that the inhibition of lysosome exocytosis from glioma cells plays an important modulatory role in their migration and invasion.
AuthorsYu Liu, Yijiang Zhou, Keqing Zhu
JournalPloS one (PLoS One) Vol. 7 Issue 9 Pg. e45910 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID23029308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Dipeptides
  • Heterocyclic Compounds, 4 or More Rings
  • LAMP1 protein, human
  • Lysosome-Associated Membrane Glycoproteins
  • Pepstatins
  • rab27 GTP-Binding Proteins
  • vacuolin-1
  • glycylphenylalanine 2-naphthylamide
  • Cathepsin D
  • RAB27A protein, human
  • rab GTP-Binding Proteins
  • pepstatin
Topics
  • Antineoplastic Agents (pharmacology)
  • Astrocytes (metabolism)
  • Cathepsin D (antagonists & inhibitors, metabolism)
  • Cell Line, Tumor (drug effects)
  • Cell Movement (drug effects)
  • Dipeptides (pharmacology)
  • Exocytosis (drug effects)
  • Gene Knockdown Techniques
  • Glioma (drug therapy, pathology)
  • Heterocyclic Compounds, 4 or More Rings (pharmacology)
  • Humans
  • Lysosome-Associated Membrane Glycoproteins (metabolism)
  • Lysosomes (drug effects, physiology)
  • Neoplasm Invasiveness
  • Pepstatins (pharmacology)
  • Protein Transport
  • RNA Interference
  • rab GTP-Binding Proteins (genetics, metabolism)
  • rab27 GTP-Binding Proteins

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