Tie2＋单核细胞在胃癌中的表达以及对裸鼠移植瘤微血管生成的作用

The expression of Tie2-expressing monocytes in gastric cancer and its effects on angiogenesis of transplanted tumor in nude mice

目的探讨Tie2+单核细胞(Tie2-expressing monocytes,TEMs)在人胃癌间质组织中的表达情况和TEMs在裸鼠的胃癌细胞移植瘤中对肿瘤增殖以及肿瘤的微血管生成的作用。方法免疫组化检测不同分期的人胃癌间质组织中Tie2+单核细胞表达;分离并培养人外周血的单核细胞,经流式分选出Tie+单核和Tie2-单核细胞,分别将人胃癌细胞(SGC7901)与Tie2+单核细胞按1:20、1:200的比例混匀、Tie2-单核细胞与人胃癌细胞按1:20比例混匀注入裸鼠皮下,单独的胃癌细胞注入裸鼠皮下作为对照,观察移植肿瘤的成瘤时间以及大小;免疫组化检测并比较各组移植瘤中CD34的表达。结果 TEMs在胃癌间质中的阳性表达率为67.3%,在Ⅰ、Ⅱ、Ⅲ、Ⅳ期的阳性率分别为0%、50.0%、78.6%、100%。其浸润的程度与胃癌TNM分期相关(P<0.05);在裸鼠移植瘤中,1:20的Tie2+单核细胞组成瘤时间快,肿瘤体积以及瘤体内CD34的表达明显大于其余浓度的Tie2+单核细胞组、Tie2-单核细胞组和单独的胃癌细胞组(P<0.05)。结论 TEMs能促进肿瘤的增殖,其促进肿瘤增殖的作用与促进肿瘤的微血管生成有关。TEMs在胃癌间质中的浸润与肿瘤分期呈正相关;胃癌组织中TEMs的浸润是不良预后的重要指标。

We aimed to explore the expression of Tie2-expressing monocytes （TEMs） in the stroma tissue of human gastric cancer and its effect on proliferation and angiogenesis of nude mouse transplanted tumor. We used immunohistochemical method to detect Tie2＋ monocytes expression in the different stages of human gastric cancer stroma tissue. And then we isolated and cultured human peripheral blood mononuclear cells for selecting Tie2＋ monocyte and Tie2- mononuclear cells by flow cytometry. Nude nice were subcutaneously injected with mix of human gastric cancer cells （SGC7901） and Tie2＋ mononuclear cells by 1：20 or 1：200, as well as the mix of Tie2- mononuclear cells and human gastric cancer cell by 1：20. Furthermore, the formation time, size and CD34 expression of the transplanted tumor were detected. The results demonstrated the positive expression rate of TEMs in gastric carcinoma stroma was 67.3%, while in phase Ⅰ、Ⅱ、Ⅲ、Ⅳ, were 0%, 50.0%, 78.6% and 100%, respectively. In the nude mouse models, we found that the 1：20 group illustrated the shortest tumorigenesis time, the biggest tumor volume, and the highest intratumoral CD34 expression level, as compared with those of the othergroups （P 〈 0.05）. Our results suggested that the TEMs can promote tumor proliferation through elevating angiogenesis in tumor. Furthermore, TEMs infiltration in the gastric cancer stroma is positively correlated withtumor stage, and may be used as an important indicator of poor prognosis.