The overall objectives of this proposed research is to understand the functional interaction of tenascin with its cellular and extracellular receptors and the role of these interactions in neoplastic growth and more specifically the processes of tumor cell migration and angiogenesis. The applicants believe that detailed knowledge of the role and mechanisms by which tenascin functions in human neoplasms will lead to a further understanding of host/tumor interactions that are recognized as important in the development of tumor invasion, metastasis and angiogenesis. Tenascin is an extracellular matrix glycoprotein whose highly restricted and regulated expression during fetal development, wound healing, the progression to malignant cancer, and its association with angiogenesis indicate a highly specialized function during these processes. These processes involve host/tumor and cell/matrix interactions which are distinctly different from the regulated stable interactions of normal cells and their tissue matrix environment.
The specific aims are: 1) to examine tenascin structure and function in tumor cell migration and endothelial cell angiogenesis; 2) characterize a new tenascin/cellular receptor phosphatase interaction which suggests a new mechanism of matrix/cell signaling; and 3) the examination of tenascin regulation and function in a unique human tumor/mouse in vivo intravital microscopy chamber model of tumor angiogenesis.
These aims reflect the intent to move from the investigation of in vitro function on the molecular and cell level to the examination of expression and function in an in vivo model. There is significant translational research potential in the proposed tenascin studies which suggest new matrix targeted diagnostic and therapeutic approaches to the control of solid tumors such as breast, prostate, and brain (glioma) cancers.
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