申请人前期研究发现RACK1是与口腔鳞癌(OSCC)侵袭转移相关的新分子(JCRCO. 2012 .138(4):563-71)，但机制需进一步阐述。肿瘤相关巨噬细胞(TAM)通过抑制免疫系统和促进血管新生从而促进肿瘤生长转移，是关系肿瘤转移和肿瘤炎症反应的关键细胞之一，近年受关注。本研究拟用细胞共培养模型、动物模型、基因芯片及生物信息学技术，就RACK1募集TAM促进OSCC生长转移的机制及其潜在临床意义进行如下研究：①确定肿瘤微环境中RACK1与TAM的关系；②RACK1对巨噬细胞M1/M2表型转化的影响；③RACK1募集的TAM对OSCC细胞生物学行为的影响；④RACK1募集TAM的相应调控信息网络和关键调控因子； ⑤RACK1蛋白及其募集TAM的关键因子为靶标的干预效果。此课题对阐明OSCC的转移机制及研发有效干预措施具有重要意义。

The results of my preliminary studies suggested RACK1 involved in the Oral squamous cell carcinoma(OSCC) metastasis（JCRCO. 2012,138(4):563-71）, but the precise mechanism is unknown. Tumor-associated macrophages (TAM) could promote tumor growth and metastasis by suppressing the immune system and enhancing angiogenesis. TAM has been drawn greater attention as one of the key cells related tumor metastasis and inflammatory response recently. Several technological means, such as cell co-culture models, animal models, gene chips and bioinformatics technology, would be used to study the mechanism of RACK1 in the recruitment of TAM to promote OSCC growth and metastasis in five areas: ① the relationship of RACK1 and TAM in tumor microenvironment; ②the role of RACK1 in the macrophage cell M1/M2 phenotypic transformation; ③ the role of RACK1 recruited TAM on the biology behavior of OSCC cell; ④the regulation mechanism of RACK1 in the recruitment of TAM; ⑤ evaluate the therapeutic efficacy of key regulatory factor in the recruitment of TAM. The implementation of this innovative project will not only help to reveal the molecular mechanisms of RACK1 in the recruitment of TAM and to let us understanding the basic biological processes of OSCC tumorigenicity and metastasis, but also provide some new ideas for the development of new tumor treatment strategies.