Microenvironment- and radiation-induced metastasis
1. Research group name/project:
Microenvironment- and radiation-induced metastasis
2. Group leader and some key members (incl. from other depts./inst.):
Einar K. Rofstad (prof.), Kjetil G. Brurberg (Post-doc), Ilana C. Benjaminsen (Post-doc), Jon-Vidar Gaustad (Ph.D. stud.), Tormod A.M. Egeland (Ph.D. stud.), Kristine Gulliksrud (Ph.D. stud.), Trude G. Simonsen (Ph.D. stud.), Christine Ellingsen (Ph.D. stud.), Camilla Mollatt (techn.), Berit Mathiesen (techn.), Kanthi Galappathi (techn.)
3. Home address on the internet:
http://radium.no/rofstad
4. Department/Institute:
Department of Biophysics, Institute for Cancer Research
4b. Hospital (HF):
Det norske radiumhospital HF
5. Main aim of research group:
The main aim of the project is to identify molecular and cellular mechanisms of microenvironment-and/or radiation-induced metastasis. Our hypothesis is that angiogenic factors and proteolytic enzymes may play important roles, whether the metastasis is caused by the tumor microenvironment, radiation therapy, or alterations in the tumor microenvironment induced by radiation therapy.
6. Some important recent results (with a few key references):
Hypoxia in the primary tumor may promote metastasis by increasing the angiogenic activity within the tissue by up-regulating the expression of interleukin-8 (Rofstad et al, Br. J. Cancer 86:301-308, 2002), and by increasing the proteolytic activity at the tumor cell surface by up-regulating the expression of urokinase-type plasminogen activator receptor (Rofstad et al, Cancer Res. 62:1847-1853, 2002). Elevated interstitial fluid pressure (IFP) in the primary tumor is associated with a high incidence of pulmonary and lymph node metastases in some tumors (Rofstad et al, Cancer Res. 62:661-664, 2002). Curative radiation therapy may promote metastasis by reducing the blood concentration of the antiangiogenic factor thrombospondin-1 (Rofstad et al, Cancer Res. 63:4055-4061, 2003). Subcurative radiation therapy may promote metastasis by increasing the fraction of hypoxic cells in the primary tumor (Rofstad et al, Cancer Res., in press, 2004). Future plans include studies of effects of low extracellular pH on metastasis.
7. Methods in current use:
Human melanomas xenografted into BALB/c-nu/nu mice are used as preclinical models of human cancer. Molecular mechanisms are studied by using cDNA microarrays and conventional methods (immunohistochemistry, Western blotting, Northern blotting). Oxygen electrodes, hypoxia markers (pimonidazole), IFP electrodes, and MRI are used to characterize the tumor microenvironment.
8. Available equipment:
Eppendorf and Oxylite oxygen electrode systems. Micropipette and wick-in-needle IFP electrode systems.
9. Some key search words:
Metastasis, radiation therapy, hypoxia, IFP, pH, angiogenesis, interleukin-8, urokinase-type plasminogen activator receptor.
Microenvironment- and radiation-induced metastasis
2. Group leader and some key members (incl. from other depts./inst.):
Einar K. Rofstad (prof.), Kjetil G. Brurberg (Post-doc), Ilana C. Benjaminsen (Post-doc), Jon-Vidar Gaustad (Ph.D. stud.), Tormod A.M. Egeland (Ph.D. stud.), Kristine Gulliksrud (Ph.D. stud.), Trude G. Simonsen (Ph.D. stud.), Christine Ellingsen (Ph.D. stud.), Camilla Mollatt (techn.), Berit Mathiesen (techn.), Kanthi Galappathi (techn.)
3. Home address on the internet:
http://radium.no/rofstad
4. Department/Institute:
Department of Biophysics, Institute for Cancer Research
4b. Hospital (HF):
Det norske radiumhospital HF
5. Main aim of research group:
The main aim of the project is to identify molecular and cellular mechanisms of microenvironment-and/or radiation-induced metastasis. Our hypothesis is that angiogenic factors and proteolytic enzymes may play important roles, whether the metastasis is caused by the tumor microenvironment, radiation therapy, or alterations in the tumor microenvironment induced by radiation therapy.
6. Some important recent results (with a few key references):
Hypoxia in the primary tumor may promote metastasis by increasing the angiogenic activity within the tissue by up-regulating the expression of interleukin-8 (Rofstad et al, Br. J. Cancer 86:301-308, 2002), and by increasing the proteolytic activity at the tumor cell surface by up-regulating the expression of urokinase-type plasminogen activator receptor (Rofstad et al, Cancer Res. 62:1847-1853, 2002). Elevated interstitial fluid pressure (IFP) in the primary tumor is associated with a high incidence of pulmonary and lymph node metastases in some tumors (Rofstad et al, Cancer Res. 62:661-664, 2002). Curative radiation therapy may promote metastasis by reducing the blood concentration of the antiangiogenic factor thrombospondin-1 (Rofstad et al, Cancer Res. 63:4055-4061, 2003). Subcurative radiation therapy may promote metastasis by increasing the fraction of hypoxic cells in the primary tumor (Rofstad et al, Cancer Res., in press, 2004). Future plans include studies of effects of low extracellular pH on metastasis.
7. Methods in current use:
Human melanomas xenografted into BALB/c-nu/nu mice are used as preclinical models of human cancer. Molecular mechanisms are studied by using cDNA microarrays and conventional methods (immunohistochemistry, Western blotting, Northern blotting). Oxygen electrodes, hypoxia markers (pimonidazole), IFP electrodes, and MRI are used to characterize the tumor microenvironment.
8. Available equipment:
Eppendorf and Oxylite oxygen electrode systems. Micropipette and wick-in-needle IFP electrode systems.
9. Some key search words:
Metastasis, radiation therapy, hypoxia, IFP, pH, angiogenesis, interleukin-8, urokinase-type plasminogen activator receptor.
Go back
Print this page
E-mail this page
