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The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells

✍ Scribed by Olivia C. Probst; Verena Puxbaum; Barbara Svoboda; Vladimir Leksa; Hannes Stockinger; Mario Mikula; Wolfgang Mikulits; Lukas Mach

Publisher
John Wiley and Sons
Year
2008
Tongue
French
Weight
279 KB
Volume
124
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

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. © 2008 Wiley‐Liss, Inc.

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