title: The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells.
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.
authors.affiliation: Institute of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Probst
authors.forename: Verena
authors.initials: V
authors.lastname: Puxbaum
authors.forename: Barbara
authors.initials: B
authors.lastname: Svoboda
authors.forename: Vladimir
authors.initials: V
authors.lastname: Leksa
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
authors.forename: Mario
authors.initials: M
authors.lastname: Mikula
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mikulits
authors.forename: Lukas
authors.initials: L
authors.lastname: Mach
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D017527:Receptor, IGF Type 2; D025521:Tumor Suppressor Proteins; D001619:beta-N-Acetylhexosaminidases