受体酪氨酸激酶RON介导胰腺癌细胞侵袭性转移的病理机制

胰腺癌是一种起病隐匿、生长迅速并以早期转移为特征的消化系统恶性肿瘤。侵袭性转移是其致死的主要原因，尤其是肝转移发生率超过50%。胰腺癌细胞侵袭性转移的机理仍不清晰。前期研究表明，受体酪氨酸激酶RON的表达和功能异常，是胰腺癌细胞形成侵袭性生长表型促进组织转移的一个关键因素，其传导的信息途径是形成高度侵袭性细胞的生物学前提。因此，本课题将以胰腺癌的原位和肝转移为模型，系统地阐述RON在癌细胞侵袭性转移中的作用，目的是阐明：①RON及其致癌型变异体在胰腺癌组织中的表达状态和侵袭性效应；②RON及其致癌型变异体介导胰腺癌细胞侵袭性生长的信息传导机理及其关键环节；③特异性抗RON单克隆抗体在阻碍胰腺癌细胞侵袭性生长和肝转移中的有效性及生物学机理。本项目的实施，对于阐明胰腺癌细胞侵袭性生长和肝转移的分子机理、验证RON作为肿瘤药靶的可行性、研制新型抗胰腺癌转移的生物药品等具有重要的理论和应用价值。

Pancreatic cancer is a digestive malignant tumor characterized by insidious onset, rapid growth and early metastasis. Invasive metastasis is the major cause of death, especially hepatic metastasis with over 50% incidence. So far, the mechanism of invasive growth and metastasis of pancreatic cancer cells remains unclear. Our recent research shown that the abnormal expression and function of receptor tyrosine kinase RON was a key factor in the invasion and metastasis of pancreatic cancer cell, while the conducted pathway was the biology prerequisite of highly invasive cell formed. Therefore, the the role of RON in cancer cell invasive growth will be explained systematically used the in situ and hepatic metastasis of pancreatic cancer as a model in this subject. The purpose is to clarify: ① the expression and invasive effect of RON and its oncogenic variants in pancreatic cancer; ② the mechanism of signal transduction and its key links of RON and its oncogenic variants mediated invasive growth of pancreatic cancer cell; ③ the effectiveness and the biology mechanism of specific anti-RON monoclonal antibody in inhibition the invasive growth and hepatic metastasis of pancreatic cancer cells. It has an important theoretical and practical values of this subject in clarifying the molecular mechanism of the invasive growth and hepatic metastasis of pancreatic cancer cells, verifying the feasibility of RON to be an anti-cancer drug target, and development of new anti-pancreatic cancer biopharmaceuticals.