The long-term goal of this research proposal is to elucidate mechanisms of breast cancer metastasis to bone. Approximately, 60-70 percent of breast cancer patients who have died or are dying of breast cancer have bone metastases. Osteonectin (OSN, SPARC, BM-40) is a bone factor that has been found to be a chemo-attractant for breast and prostrate cancer cells. In addition, increased OSN expression has been found in breast cancer, however a connection between increased OSN expression in breast cancer cells and bone metastasis has not been proven. Surprisingly, a cell surface receptor has yet to be identified. This proposal will test the central hypothesis that increased expression of OSN in breast cancer cells increases tumor growth and metastasis to bone, and binding of OSN to its cell surface receptor is important for this process.
Specific aim 1 will determine if altered expression of OSN in breast cancer cells will affect tumor cell growth, invasion and protease activity in vitro and specific aim 2 will examine if this altered expression of OSN affects tumor cell growth in the mammary fat pad, in bone and in metastasis to bone in vivo.
Specific aim 3 will establish if OSN binds to the cell surface and characterize the cell surface binding protein. A variety of approaches will be utilized to elucidate the role OSN in breast cancer bone metastasis and to identify OSN surface binding proteins. Identification of the OSN binding protein and determining the role of endogenous production of OSN by breast cancer cells may lead to better diagnostic and/or therapeutic approaches for breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA091572-02
Application #
6685697
Study Section
Special Emphasis Panel (ZRG1-SSS-N (20))
Program Officer
Lohrey, Nancy
Project Start
2001-11-16
Project End
Budget Start
2002-11-16
Budget End
2003-11-15
Support Year
2
Fiscal Year
2003
Total Cost
$45,320
Indirect Cost
Name
U.S. Nat'L Institute/Dental/Craniofacial Research
Department
Type
DUNS #
015683162
City
Bethesda
State
MD
Country
United States
Zip Code
20892
Koblinski, Jennifer E; Kaplan-Singer, Benjamin R; VanOsdol, Sherilyn J et al. (2005) Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis. Cancer Res 65:7370-7
Koblinski, Jennifer E; Wu, Michael; Demeler, Borries et al. (2005) Matrix cell adhesion activation by non-adhesion proteins. J Cell Sci 118:2965-74