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The mannose 6‐phosphate/insulin‐like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells
Author(s) -
Probst Olivia C.,
Puxbaum Verena,
Svoboda Barbara,
Leksa Vladimir,
Stockinger Hannes,
Mikula Mario,
Mikulits Wolfgang,
Mach Lukas
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24236
Subject(s) - insulin like growth factor 2 receptor , biology , mannose 6 phosphate , growth factor , cancer research , transfection , mannose receptor , cancer cell , endocytosis , cell , cell culture , insulin like growth factor 1 receptor , receptor , cancer , in vitro , macrophage , biochemistry , genetics
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.