Malignant ovarian tumors with induced expression of carbonyl reductase show spontaneous regression.
Malignant ovarian tumors with induced expression of carbonyl reductase show spontaneous regression.
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DOI：
10.4137/cmo.s9005
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Mizunuma H
中科院分区：
文献类型：
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作者：
Wang H;Yokoyama Y;Tsuchida S;Mizunuma H
本研究利用羰基还原酶（CR）表达增加的小鼠卵巢癌细胞，在肿瘤模型中研究了肿瘤的增殖。通过脂质转染将CR cDNA转染到小鼠T-Ag-MOSE卵巢癌细胞中。将转染CR的细胞（CR诱导组）或空载体处理的细胞（对照组）按0.5 × 106 / 0.2 mL的浓度注射到8周龄裸鼠背部，观察两组小鼠肿瘤增殖5周。观察5周，对照组肿瘤体积增大。而CR诱导组肿瘤体积在第2周呈上升趋势，但在第5周呈下降趋势。两组肿瘤生长曲线差异有统计学意义（Mann-Whitney U检验，P < 0.001）。采用第三周分离的肿瘤组织进行组织学和生化实验。CR诱导组肿瘤出现坏死和炎性细胞浸润。与对照组相比，CR诱导组的凋亡细胞数量显著增加（P < 0.001）。乳脂球EGF因子8是巨噬细胞等吞噬细胞的“吃我”信号，在CR诱导组的肿瘤细胞质和间质细胞中广泛表达，观察到巨噬细胞吞噬凋亡细胞。与对照组相比，CR诱导组肿瘤中血管内皮生长因子的表达明显降低。乳脂球EGF因子8增加所吸引的吞噬细胞吞噬凋亡细胞导致的坏死增加被认为是CR诱导组自发肿瘤消退的机制。
The present study investigated tumor proliferation in a tumor model using murine ovarian cancer cells with increased carbonyl reductase (CR) expression. CR cDNA was transfected into murine T-Ag-MOSE ovarian cancer cells by lipofection. CR-transfected cells (CR induction group) or empty vector-treated cells (control group) were injected into the backs of 8-week-old nude mice at a concentration of 0.5 × 106 per 0.2 mL. Subsequent tumor proliferation in both groups was observed for 5 weeks. The control group showed an increase in tumor volume during the 5 weeks of observation. However, tumor volume in the CR induction group increased up to the second week but then decreased continuously until the fifth week of observation. The tumor growth curves for the two groups showed a significant difference (Mann-Whitney U test, P < 0.001). Histological and biochemical experiments were performed using tumor tissues isolated in the third week. Necrosis and inflammatory cell infiltration were noted for tumors in the CR induction group. Also, the number of apoptotic cells was significantly increased in the CR induction group compared with the control group (P < 0.001). Milk fat globule EGF factor 8, an “eat-me” signal for phagocytes such as macrophages, was expressed extensively in the tumor cytoplasm and interstitial cells of the CR induction group, and engulfment of apoptotic cells by macrophages was observed. Vascular endothelial growth factor expression in tumors was notably decreased in the CR induction group compared with the control group. Increased necrosis due to engulfing of apoptotic cells by phagocytes attracted by increased milk fat globule EGF factor 8 was considered to be the mechanism of spontaneous tumor regression in the CR induction group.