活化CD8+ T细胞来源的Exosomes通过Fas/MMP9途径促进肿瘤转移及其相关机制的研究

Almost all kinds of tumor cells express Fas receptor, however activation of Fas signal can not induce tumor cells apoptosis but promote their progress.During the activation of CD8+ T cells, they secret large amount of FasL expressed exosomes, which show potential biological function and can induce apoptosis of T lymphocytes. We suppose that FasL expressed exosomes from activated CD8+ T cells can also activate Fas signal of tumor cells and subsequently promote tumor metastasis. In this project, we will isolate exosomes from activated CD8+ T cells and confirm whether they can increase tumor cells to express MMP9 by Fas pathway. Moreover, we will also separate the counterpart exosomes in tumor-bearing mice and confirm their function of promoting tumor metastasis, which can demonstrate the physiologic existence of this kind of exosomes. Results of this project will reveal a novel mechanism of tumor metastasis and thereby provide a whole new idea for tumor therapy.

许多肿瘤细胞表达Fas受体，但Fas信号的活化不但不引起肿瘤细胞凋亡，反促进肿瘤进展。研究表明，Fas信号活化能促进肿瘤细胞MMP9表达，增强肿瘤侵袭能力，促进其转移。活化CD8+T淋巴细胞在活化过程中分泌大量表达FasL的Exosomes，这一形式存在的FasL具有完整生物学功能，能诱导淋巴细胞凋亡。因此我们推测活化CD8+T淋巴细胞分泌的表达FasL的Exosomes亦能促进肿瘤细胞Fas信号活化，从而促进肿瘤转移。本项目通过制备活化CD8+T淋巴细胞来源的Exosomes，检测其是否能通过Fas信号促进肿瘤细胞MMP9表达，增强肿瘤细胞的侵袭与转移能力并对其机制进行研究；此外，我们还将从荷瘤小鼠体内分离该群Exosomes，明确其促肿瘤转移功能，从而证实促肿瘤转移Exosomes的生理存在。本课题的开展将从一全新角度揭示肿瘤转移机制，从而为探索一种有效的肿瘤治疗方法提供新的思路。

许多肿瘤细胞表达Fas受体，但Fas信号的活化不但不引起肿瘤细胞凋亡，反促进肿瘤进展。研究表明，Fas信号活化能促进肿瘤细胞MMP9表达，增强肿瘤侵袭能力，促进其转移。活化CD8+T淋巴细胞在活化过程中分泌大量表达FasL的Exosomes，这一形式存在的FasL具有完整生物学功能，能诱导淋巴细胞凋亡。因此我们推测活化CD8+T淋巴细胞分泌的表达FasL的Exosomes亦能促进肿瘤细胞Fas信号活化，从而促进肿瘤转移。本项目制备活化CD8+T淋巴细胞来源的Exosomes，发现其能通过Fas信号促进肿瘤细胞MMP9表达，增强肿瘤细胞的侵袭与转移能力并对其机制进行了研究；此外，我们还从荷瘤小鼠体内分离该群Exosomes，明确其促肿瘤转移功能，从而证实促肿瘤转移Exosomes的生理存在。本课题的开展从一全新角度揭示肿瘤转移机制，从而为探索一种有效的肿瘤治疗方法提供新的思路。