Multiple myeloma is a universally fatal disease characterized by the accumulation of malignant plasma cells in the bone marrow. Because of the ability of IL-6 to drive myeloma cell proliferation, the investigator's previous studies focused on the molecular changes that result in deregulation of tumor cell IL-6 expression. The study proposed in this application is based on two hypotheses, 1) that overexpression of the IGF-I receptor is a crucial component of the altered IL-6 responsiveness of myeloma cells; 2) that IL-6 stimulates myeloma cell IGF and IGF-I-R expression, thereby further potentiating tumor cell growth. To test these hypotheses, the investigator will 1) determine the mechanism by which anti-IGF-I-R mABs inhibit IL-6-stimulated myeloma cell proliferation; 2) determine the role of IGF-I receptor expression in IL-6-mediated myeloma cell growth; and 3) determine the mechanism(s) underlying overexpression of the IGF-I receptor in myeloma cells. Information obtained from these studies has the potential to provide important insight into the genetic events that occur during tumor progression in myeloma patients, and also may facilitate determination of which patients are in need or more aggressive therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA062228-06
Application #
6172645
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Finerty, John F
Project Start
1995-04-01
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
6
Fiscal Year
2000
Total Cost
$203,982
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Mihalcik, Stephen A; Huddleston 3rd, Paul M; Wu, Xiaosheng et al. (2010) The structure of the TNFRSF13C promoter enables differential expression of BAFF-R during B cell ontogeny and terminal differentiation. J Immunol 185:1045-54