淋巴细胞-肿瘤细胞cell-in-cell介导MAPK信号途径对结直肠癌侵袭转移的影响及机制

Cell-in-cell is the phenomenon that homotypic and heterotypic cells can enter other cells actively and function in the target cells, however, the impact on tumor is not clear. We have reported cell-in-cell between immune cells and colon cancer and apoptotic death of immune cells which requires granzyme B in the target cells in our previous study. Cell-in-cell can lead to genetic information exchange and change the phenotypic characteristics.Our recent preliminary experiment showed increased proliferative activity in cell-in-cells. Meanwhile, we have reported MAPK pathway, which activates granzyme B in immune cells, plays an important role in colorectal cancer malignant progression. Our recent preliminary experiment showed cell-in-cell could acquire high level of MAPK pathway.Can cell-in-cell bwtween lymphocytes and tumor cells in colorectal cancer acquire acivated MAPK pathway by genetic information exchange to affect invasion, metastasis and prognosis in colorectal cancer? Based on our previous research, from association analysis of population to in vitro and in vivo experiments, we are aimed to analyze the impact of cell-in-cell bwtween lymphocytes and tumor cells in colorectal cancer on invasion, metastasis and prognosis, to analyze the mechanism, to disclose the new mechanism of immune escape in colorectal cancer.

Cell-in-cell即同种或异种活细胞主动进入另一个细胞并在其中活动的现象，在肿瘤中的影响尚不清楚。我们前期报道免疫细胞-结肠癌细胞间cell-in-cell，免疫细胞发生granzyme B参与的凋亡样死亡。Cell-in-cell发生遗传信息交换从而改变靶细胞表型特征，近期预实验表明cell-in-cell肿瘤细胞增殖活性更强。同时我们前期报道MAPK途径对结直肠癌恶性发展有重要作用，而免疫细胞granzyme B的激活依赖MAPK途径，近期预实验表明cell-in-cell细胞可以获得高表达的MAPK途径。淋巴细胞-肿瘤细胞cell-in-cell可否通过遗传信息交换激活MAPK途径从而影响结直肠癌侵袭转移及预后？我们拟在前期基础上,从人群关联分析到体外、体内实验分析淋巴细胞-肿瘤细胞cell-in-cell对结直肠癌侵袭转移及预后的影响及机制，揭示结直肠癌免疫逃避新的机制。

Cell-in-cell即同种或异种活细胞主动进入另一个细胞并在其中活动的现象，在肿瘤中的影响尚不清楚。本项目我们揭示了淋巴细胞主动钻入结直肠癌肿瘤细胞的cell-in-cell过程，体外分选了发生淋巴细胞钻入的结直肠癌肿瘤细胞；体内、体外实验揭示了淋巴细胞-肿瘤细胞的cell-in-cell过程促进了结直肠癌细胞侵袭转移,淋巴细胞杀伤能力无明显差异；提出高cell-in-cell(大于5.2/高倍视野) 总生存（overall survival，OS）、无病生存（disease free survival，DFS）更差，；淋巴细胞-肿瘤细胞间cell-in-cell过程促进结直肠癌侵袭转移依赖于MAPK信号途径P38磷酸化。本项目首次揭示了淋巴细胞-肿瘤细胞cell-in-cell对结直肠癌侵袭转移的影响，阐明了结直肠癌侵袭转移新的机制，首次提出cell-in-cell计数可作为Ⅰ-Ⅲ期结直肠癌预后指标，首次揭示了MAPK信号途径在淋巴细胞-肿瘤细胞间cell-in-cell促进结直肠癌侵袭转移中的分子机制。