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

我们用病理学技术显示了甲状旁腺激素相关蛋白(PTHrP)和骨桥蛋白受体αvbeta3整合素的冰前组织定位。在一系列临床病理研究中，我们发现α-β_3整合素的表达，尤其是β_3整合素亚基的表达可能在组织特异性的确定中起重要作用。此外，在使用手术和尸检标本的其他一系列研究中，我们表明肿瘤来源的PTHrP有助于成骨细胞产生破骨细胞。因此，产生PTHrP的荷瘤宿主有更大的风险出现骨表面侵蚀。骨桥蛋白是主要的骨基质蛋白之一，因此存在于Roded骨表面。Alphavbeta3整合素正是结合在这个Ostopontin上。综上所述，表达PTHrP和αvbeta3整合素的肿瘤细胞可以更好地在骨的微环境中附着和存活，在进行这些组织病理学研究时，需要更敏感和特异的原位杂交方法。在通过RT-PCR等生化研究证实我们的组织形态数据的同时，我们开发了以溴脱氧尿苷为半抗原的高灵敏的原位杂交系统。我们已经在各种国际会议和国内会议上公布了我们的数据，并为学术会议出版了许多科学论文。

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.