Exosomes在涎腺腺样囊性癌侵袭转移中的作用及机制研究

Salivary adenoid cystic carcinoma (SACC) is remarkable for its invasion, high rates of recurrence, and lung metastasis. Our group had reported that the up-regulation of p-Smad2 in primary tumors is associated with human SACC metastasis. Exosomes are molecular complex intercellular signaling organelles with multiple functions. We have evidenced that exosomes promots the motility of SACC-83 cells in the preliminary experiment in vitro. The increase in motility induced by exosomes was accompanied by the activation of p-Smad2, so we infer that exosomes may play a crucial role in the invasion and lung metastasis of SACC. We plan to study the role of exosomes and signalling pathway concerned in the key invasion and metastasis stages of SACC. We also plan to analyse component part in the exosomes for finding out the key synergic molecules, which will be confirmed in saliva to see if it can be a biomarker of SACC. Finally, we intend to examine its relationship with TGF-β, which had been reported by us as a candidate biomarker in the invasion and lung metastasis of SACC. The results of this study will elucidate the molecular mechanism of SACC invasion and lung metastasis from the point of view of exosomes. Exosomes may be a promising target for the treatment of invasion and metastasis of SACC as well as a biomarker of clinical diagnosing, staging and prediction prognosis.

涎腺腺样囊性癌（SACC）侵袭性强且易发生肺转移，本课题组已发现p-Smad2上调是SACC肺转移标志之一。Exosomes是细胞间信息传递的重要单位，具有作用距离远、外周循环稳定等特点；我们预实验发现exosomes促进SACC细胞运动性的同时上调p-Smad2，提示exosomes可能与SACC侵袭转移有关。本课题拟在SACC侵袭和转移关键环节研究exosomes所起作用及通过的相关信号通路；分析exosomes的成分，找出对SACC肺转移起协同作用的关键分子，并对唾液中exosomes中相应分子进行检测，验证其是否可作为SACC诊断和预后标记；最后研究在SACC肺转移中起重要作用的TGF-β对exosomes分泌和摄取的影响，并分析其机制。本研究将首次从exosomes角度阐明SACC侵袭性强易肺转移的生物学特点，为靶向治疗SACC侵袭转移提供靶点和诊断、预后标记。

涎腺腺样囊性癌（SACC）侵袭性强且易发生肺转移。Exosomes是细胞间信息传递的重要单位，具有作用距离远、外周循环稳定等特点；我们实验结果表明exosomes促进SACC细胞迁移和侵袭，促进抵抗凋亡的能力，同时Exosomes上调p-smad2, p-JNK和p-ERK的表达。Exosomes促进HUVEC细胞的迁移和侵袭能力。体内和体外实验表明exosomes促进HUVEC细胞的血管形成能力。这些结果表明腺样囊性癌细胞分泌的exosomes可能在SACC血管形成和转移中起重要作用。