Document Detail

The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells.
MedLine Citation:
PMID:  19195023     Owner:  NLM     Status:  MEDLINE    
The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) mediates biosynthetic sorting and endocytosis of various factors that impinge on the proliferation, migration and invasiveness of tumour cells. The gene encoding M6P/IGF2R is frequently lost or mutated in a wide range of malignant tumours including squamous cell carcinomas. We have previously shown that M6P/IGF2R-deficient SCC-VII murine squamous cell carcinoma cells secrete large amounts of pro-invasive lysosomal proteinases. Furthermore, the formation of mature lysosomes is impaired in SCC-VII cells. To assess the link between M6P/IGF2R status and tumour invasion, we have now generated SCC-VII lines stably transfected with human M6P/IGF2R cDNA. Reconstitution of functional M6P/IGF2R expression in SCC-VII cells strongly improves the intracellular retention of lysosomal proteinases and restores the formation of mature lysosomes. In addition, the presence of heterologous M6P/IGF2R compromises the growth of SCC-VII cells both in vitro and in vivo. Remarkably, M6P/IGF2R expression also reduces the invasive capacity of SCC-VII cells in response to various chemoattractants. These results indicate that the M6P/IGF2R status influences the metastatic propensity of squamous cell carcinomas.
Olivia C Probst; Verena Puxbaum; Barbara Svoboda; Vladimir Leksa; Hannes Stockinger; Mario Mikula; Wolfgang Mikulits; Lukas Mach
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  124     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2559-67     Citation Subset:  IM    
Institute of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
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MeSH Terms
Carcinoma, Squamous Cell / pathology*
Cell Proliferation
Extracellular Matrix / physiology
Lysosomes / enzymology
Mice, SCID
Neoplasm Invasiveness
Receptor, IGF Type 2 / analysis,  physiology*
Tumor Suppressor Proteins / physiology
beta-N-Acetylhexosaminidases / metabolism
Reg. No./Substance:
0/Receptor, IGF Type 2; 0/Tumor Suppressor Proteins; EC

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