It has been discovered that the NH2-terminal sequence of a major secreted phosphoprotein associated with neoplastic transformation is identical to that of the bone matrix protein osteopontin (Op). Traditionally, Dr. Butler's group has been involved in the purification and characterization of noncollagenous proteins from demineralized bone matrix. Recent efforts have been focused on the structure and function of Op, a phosphorylated matrix glycoprotein of 41.5 kDa that has several distinct structural domains, one of which contains an RGD sequence recognized by the family of cell adhesion receptors known as integrins. Op has been shown to promote long-term attachment of osteoblasts in vitro. I hypothesize that the """"""""turn on"""""""" in Op production during tumorigenic transformation is associated with alterations of adhesion properties of neoplastic cells and that the levels of circulating Op might correlate with the presence or status of certain tumors including osteosarcoma. Along these lines, the distribution of Op anchored in the extracellular matrix of both normal and neoplastic tissues might correlate with the growth and/or metastatic potential of the tumor. My first objective is to develop a radioimmunoassay for serum Op. My second objective is to use the RIA to study the feasibility of following circulating Op levels as an index of tumor burden. My third objective is to use immunohistochemical and in situ hybridization techniques to examine the presence and distribution of Op in various tumors. These studies should assist me in reaching my long term goal of understanding the role of Op in neoplastic tissue and determining if the detection of Op in serum or tissue sections can serve as a diagnostic tool.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Unknown (K15)
Project #
5K15DE000309-03
Application #
3088646
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1991-03-01
Project End
1996-02-29
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Dentistry
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225