Mannose 6-phosphate/IGF-II receptor: a multifunctional protein with anti-metastatic potential
Abstract
The spread of neoplastic cells from a primary tumour to distant sites represents a major obstacle in current cancer therapies. During formation of such metastases, tumour cells have to penetrate different tissue barriers and then to migrate to other organs within the affected body. Substances which block the migratory propensity of malignant tumour cells could be used to treat cancer patients. This project has dealt with the anti-metastatic potential of the multifunctional protein, mannose 6-phosphate/IGF-II receptor (M6P/IGF2R), since various M6P/IGF2R ligands seem to play a significant role in tumour invasion and metastasis. A better understanding of the role of M6P/IGF2R and its interaction partners in the formation of metastases is a prerequisite for the development of treatment regimens based on prevention of the biological activities of these ligands. This project has focussed on the individual relevance of various M6P/IGF2R ligands for the anti-metastatic potential of the receptor. It could be demonstrated that the capacity to interact with IGF-II and plasmin is dispensable for this property of M6P/IGF2R. Furthermore, it was shown that the recently discovered M6P/IGF2R ligand and potential tumour suppressor, Cellular Repressor of E1A-stimulated Genes, carries mannose 6-phosphate residues and behaves like a classical lysosomal protein. In addition, it was elucidated why lysosomal transport via mannose 6-phosphate receptors often displays unusual features in tumour cells.
Publikationen
The 46-kDa mannose 6-phosphate receptor does not depend on endosomal acidification for delivery of hydrolases to lysosomes.
Autoren: Probst, OC; Ton, P; Svoboda, B; Gannon, A; Schuhmann, W; Wieser, J; Pohlmann, R; Mach, L Jahr: 2006
Journal articles
Lysosomal proteinases and their receptors: the ability of M6P/IGF2R to bind mannose 6-phosphate is critical for its capacity to restrict the invasiveness of tumour cells
Autoren: Probst, O.C., Puxbaum, V., Karayel, E., Bäuerl, C., Schida, N., Svoboda, B., Mach, L. Jahr: 2008
Conference & Workshop proceedings, paper, abstract
Project staff
Lukas Mach
Univ.Prof. Dipl.-Ing. Dr.nat.techn. Lukas Mach
lukas.mach@boku.ac.at
Tel: +43 1 47654-94065, 94360
Project Leader
01.04.2006 - 31.03.2007