The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells.
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.
Probst
Olivia C
OC
Institute of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
Puxbaum
Verena
V
Svoboda
Barbara
B
Leksa
Vladimir
V
Stockinger
Hannes
H
Mikula
Mario
M
Mikulits
Wolfgang
W
Mach
Lukas
L
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
D017527:Receptor, IGF Type 2; D025521:Tumor Suppressor Proteins; D001619:beta-N-Acetylhexosaminidases