EMMPRIN介导肿瘤微环境在涎腺腺样囊性癌演进中的作用及机制研究

Salivary adenoid cystic carcinoma (SACC) has characteristic progression with perineural invasion and distance lung metastasis, which result to poor prognosis even die. The special progression of SACC has become the research hotspot of the head and neck tumor. However, there is little study about the multidirectional and dynamic effects of the tumor microenvironment on the tumor progression of SACC. EMMPRIN is a new molecule involved in tumor microenvironment. EMMPRIN mediated the interactions between the tumor cells with the carcinoma-associated fibroblasts (CAFs) and the extracellular matrix (ECM), and thus regulated the tumor progression. Our recent studies found EMMPRIN is involved in the invasion and metastasis of SACC, and played a critical role in the tumor progression. In the present study, we aimed to study the EMMPRIN mediated multidirectional interactions between SACC with CAFs or ECM. Intervention of RNAi and models of co-culture model, 3D culture model, perineural invasion model, lung metastasis model were used to study the temporal and spatial effects of EMMPRIN mediated tumor microenvironment on the progression of SACC. Examinations of RT-PCR, western blot, laser capture microdissection, tissue chip and gene chip were employed to explore the mechanism. This study will not only elucidate the special progression of SACC, but also provide new strategy for the basic research and clinical treatment of SACC.

涎腺腺样囊性癌(SACC)的独特演进过程，尤其是嗜神经侵袭和远处肺转移，常导致患者预后较差甚至死亡，是头颈肿瘤研究领域的热点和难点。而目前尚无多向动态阐释肿瘤微环境对SACC演进影响的研究。EMMPRIN是最新发现的肿瘤微环境关键调节子，通过介导肿瘤细胞与癌相关成纤维细胞(CAFs)及细胞外基质(ECM)间的相互作用，调控肿瘤演进过程。我们的前期研究证实EMMPRIN是SACC侵袭转移相关分子，与其演进过程密切相关。本项目旨在以EMMPRIN多向介导SACC与CAFs及ECM的相互作用为合理切入点。采用基因干扰和共培养、3D培养、嗜神经侵袭及肺转移模型，动态研究EMMPRIN介导肿瘤微环境的时空变化特点及其对SACC演进的作用。并进一步通过RT-PCR、WB、激光俘获切割、组织及基因芯片等方法阐明相关作用机制。从而深入分析SACC的独特演进过程，并为SACC的基础研究和临床治疗提供新策略。

涎腺腺样囊性癌(SACC)具有嗜神经侵袭和远处肺转移的特性，常导致患者预后较差甚至死亡，是头颈肿瘤研究领域的焦点。而目前尚无多向动态阐释肿瘤微环境对SACC 演进影响的研究。EMMPRIN 是最新发现的肿瘤微环境关键调节子，通过介导肿瘤细胞与癌相关成纤维细胞(CAFs)及细胞外基质(ECM)间的相互作用，调控肿瘤演进过程。我们的前期研究证实EMMPRIN 是SACC 侵袭转移相关分子，与其演进过程密切相关。本项目以EMMPRIN 多向介导SACC 与CAFs 及ECM 的相互作用为合理切入点。采用基因干扰和共培养、3D 培养、嗜神经侵袭及肺转移模型，动态研究了EMMPRIN 介导肿瘤微环境的时空变化特点及其对SACC 演进的作用。并进一步通过RT-PCR、WB、激光俘获切割、组织及基因芯片等方法阐明相关作用机制。从而深入分析了SACC 的独特演进过程，为SACC演进的研究提供了实验依据。