Importance of S100A4 in cancer metastases
1. Research group name/project:
Importance of S100A4 in cancer metastases
2. Group leader and some key members (incl. from other depts./inst.):
GM Mælandsmo (senior scientist), K Flatmark (postdoc), K Andersen (PhD student), KB. Pedersen (PhD student), H Rasmussen (technician), T Øyjord (technician), S Sjøli (student), MH Haugen (student)
3. Home address on the internet:
https://www.ous-research.no/malandsmo
4. Department/Institute:
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital
5. Main aim of research group:
The calcium-binding protein S100A4 has been postulated to promote metastasis formation. The main purpose of the project is to study the molecular mechanisms behind some of the different biological functions that have been suggested for S100A4, and investigate how these functions might have impact on the metastatic phenotype.
6. Some important recent results (with a few key references):
By employing ribozyme-mediated downregulation of S100A4 we observed a nearly complete reversal of the metastatic phenotype (Mælandsmo: Cancer Res 1996). An important parameter for the cells ability to metastasize is their capacity to degrade the basement membrane, and a functional link between matrix metalloproteinase-activity (MMP) and S100A4 has been detected (Bjørnland: Cancer Res 2000). The prognostic importance of S100A4 has been studied, and a correlation between expression and prognostic factors indicating poor prognosis was found in breast (Pedersen: Br J Cancer 2001) and colorectal cancer (Flatmark: J Pathol 2003), as well as malignant melanomas (Andersen et al: submitted). We have obtained results showing that S100A4 added extracellularly can sensitize cancer cells for certain types of apoptosis (Pedersen: submitted), and that the protein can be localized in the nucleus (Flatmark: J Pathol, 2003). In ongoing work we study protein localization, interacting protein partners and downstream regulatory pathways leading to the observed biological effects.
7. Methods in current use:
Cell culture experiments including in vitro invasion assay. Molecular biology methods including Northern and Western blotting, as well as microarray hybridization and PCR. Assays measuring cell viability and apoptosis, immunohistochemistry, confocal microscopy, in vivo assays measuring tumorigenicity and metastatic ability.
8. Available equipment:
9. Collaborators:
9.1. Among Helse Sør hospitals : JM Nesland (prof, Dept of Pathol), J Wesche (senior sci, Dept of Biochem), SO Mikalsen (senior sci, LAMYK), D Warren (senior sci, Central Lab), all DNR; K Bjørnland (postdoc Surg Dept Rikshosp)
9.2. Other Norwegian collaborators: JO Winberg, Biochem Dept, Univ of Tromsø
9.3. Collaborators from other countries: Lewis Pannell (prof), Proteom and Mass Spec Facility, Univ of South Alabama, USA; Danna Zimmer (prof), Collage of Vet Med, Texas A&M Univ, USA, MH Le Du (senior sci), Protein Struc Lab, Cedex, France
10. Some key search words:
Ca-binding protein, S100-protein, protein interactions, apoptosis (NF-kB, ROS), internalization, signal transduction, metastases, osteosarcoma, melanoma, breast-and colorectal carcinoma, MMP, TIMP
Importance of S100A4 in cancer metastases
2. Group leader and some key members (incl. from other depts./inst.):
GM Mælandsmo (senior scientist), K Flatmark (postdoc), K Andersen (PhD student), KB. Pedersen (PhD student), H Rasmussen (technician), T Øyjord (technician), S Sjøli (student), MH Haugen (student)
3. Home address on the internet:
https://www.ous-research.no/malandsmo
4. Department/Institute:
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital
5. Main aim of research group:
The calcium-binding protein S100A4 has been postulated to promote metastasis formation. The main purpose of the project is to study the molecular mechanisms behind some of the different biological functions that have been suggested for S100A4, and investigate how these functions might have impact on the metastatic phenotype.
6. Some important recent results (with a few key references):
By employing ribozyme-mediated downregulation of S100A4 we observed a nearly complete reversal of the metastatic phenotype (Mælandsmo: Cancer Res 1996). An important parameter for the cells ability to metastasize is their capacity to degrade the basement membrane, and a functional link between matrix metalloproteinase-activity (MMP) and S100A4 has been detected (Bjørnland: Cancer Res 2000). The prognostic importance of S100A4 has been studied, and a correlation between expression and prognostic factors indicating poor prognosis was found in breast (Pedersen: Br J Cancer 2001) and colorectal cancer (Flatmark: J Pathol 2003), as well as malignant melanomas (Andersen et al: submitted). We have obtained results showing that S100A4 added extracellularly can sensitize cancer cells for certain types of apoptosis (Pedersen: submitted), and that the protein can be localized in the nucleus (Flatmark: J Pathol, 2003). In ongoing work we study protein localization, interacting protein partners and downstream regulatory pathways leading to the observed biological effects.
7. Methods in current use:
Cell culture experiments including in vitro invasion assay. Molecular biology methods including Northern and Western blotting, as well as microarray hybridization and PCR. Assays measuring cell viability and apoptosis, immunohistochemistry, confocal microscopy, in vivo assays measuring tumorigenicity and metastatic ability.
8. Available equipment:
9. Collaborators:
9.1. Among Helse Sør hospitals : JM Nesland (prof, Dept of Pathol), J Wesche (senior sci, Dept of Biochem), SO Mikalsen (senior sci, LAMYK), D Warren (senior sci, Central Lab), all DNR; K Bjørnland (postdoc Surg Dept Rikshosp)
9.2. Other Norwegian collaborators: JO Winberg, Biochem Dept, Univ of Tromsø
9.3. Collaborators from other countries: Lewis Pannell (prof), Proteom and Mass Spec Facility, Univ of South Alabama, USA; Danna Zimmer (prof), Collage of Vet Med, Texas A&M Univ, USA, MH Le Du (senior sci), Protein Struc Lab, Cedex, France
10. Some key search words:
Ca-binding protein, S100-protein, protein interactions, apoptosis (NF-kB, ROS), internalization, signal transduction, metastases, osteosarcoma, melanoma, breast-and colorectal carcinoma, MMP, TIMP