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.
| Devoll, R E; Li, W; Woods, K V et al. (1999) Osteopontin (OPN) distribution in premalignant and malignant lesions of oral epithelium and expression in cell lines derived from squamous cell carcinoma of the oral cavity. J Oral Pathol Med 28:97-101 |
| Devoll, R E; Pinero, G J; Appelbaum, E R et al. (1997) Improved immunohistochemical staining of osteopontin (OPN) in paraffin-embedded archival bone specimens following antigen retrieval: anti-human OPN antibody recognizes multiple molecular forms. Calcif Tissue Int 60:380-6 |
