THE ROLE OF PTHrP AND INTEGRIN BETA3 SUBUNIT IN THE DEVELOPMENT OF SKELETAL METASTASES

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We have shown presice histological localization of parathyroid hormone-related protein (PTHrP) and alphavbeta3 integrin, a receptor for the osteopontine, by pathological technique. In a series of the clinico-pathological studies, we showed that the expression of the alphavbeta3 integrin, especially beta3 integrin subunit might play an important role in the definition of the tissue specificity. Futhermore, in other series of studies using surgical and autopsy specimens, we showed that the tumor-derived PTHrP served to help the osteoblastic cell to generate the osteoclasts. As a result, PTHrP producing tumor-bearing host had a greater risk to have a eroded bone surface. The osteopontine, one of the major bone-residing bone matrix proteins, is, therfore, present at the site of roded bone surface. It is this ostopontine that the alphavbeta3 integrin is bond to. Taken together, tumor cell expressing PTHrP and alphavbeta3 integrin can have a better chance to attach and survive in a microenviroment of the bone.During performing these histopathological studies, more sensitive and specific method for in situ hybridization was neccessory. While confirming our histomorphological data by biochemical studies as RT-PCR,we have developed highly sensitive in situ hybridization system using a bromodeoxyuridine as a hapten. We have presented our data at various international congress as well as domestic meetings, and publish a lot of scientific papaers for academic jurnals.