The focus of this proposal is to define the functional role of the matrix metalloprotease (MMP) Stromelysin-1 in squamous cell carcinoma progression. Stromelysin-1 is a major extracellular matrix (ECM) degrading proteinases implicated in a variety of normal and pathological cellular processes including tumor cell invasion. There is focused attention on defining the particular roles of individual MMP in order to appropriately modulate their activity in a clinical setting with the use of MMP inhibitors. Understanding not only the role of individual MMPs in tumor progression, but additionally the distinct roles of host/stromal and tumor MMP expression is a fundamental unanswered question the matrix protease field. We have evidence that stromelysin-1 expression can play dual roles during tumor progression, meaning that expression of stromelysin-1 during early stages of tumor progression is protective whereas tumor expression of stromelysin-1 is intimately involved in generating an invasive phenotype in squamous cell carcinoma. Current experimental cancer therapy models include the use of MMP inhibitors. Thus, we need to well define the role of stromelysin-1 at each stage of tumor progression in order to predict how loss of stromelysin-1 will effect tumor development and invasiveness. The studies outlined in the research proposal will provide novel insight into the role of Stromelysin-1 during tumor progression and provide an in vivo model for testing of MMP inhibitors in a clinical setting.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA084642-02
Application #
6377729
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (01))
Program Officer
Lohrey, Nancy
Project Start
2001-04-30
Project End
Budget Start
2001-04-30
Budget End
2002-04-29
Support Year
2
Fiscal Year
2001
Total Cost
$40,196
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
McCawley, Lisa J; Crawford, Howard C; King Jr, Lloyd E et al. (2004) A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Res 64:6965-72
Leite-Browning, Maria L; McCawley, Lisa J; Jahnen-Dechent, Willi et al. (2004) Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis. Int J Oncol 25:319-24
Leite-Browning, Maria L; McCawley, Lisa J; Choi, Oksoon H et al. (2002) Interactions of alpha2-HS-glycoprotein (fetuin) with MMP-3 and murine squamous cell carcinoma cells. Int J Oncol 21:965-71