CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer.
CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer.
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DOI：
10.1002/cam4.478
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发表时间：
2015-09
期刊：
影响因子：
4
通讯作者：
Hase K
中科院分区：
文献类型：
--
作者：
Yoshida K;Tsujimoto H;Matsumura K;Kinoshita M;Takahata R;Matsumoto Y;Hiraki S;Ono S;Seki S;Yamamoto J;Hase K
CD 47是一种抗吞噬分子，通过连接作用于吞噬细胞上的信号调节蛋白α;最近已报道其增强的表达和治疗靶向用于几种恶性肿瘤。然而，CD 47在胃癌中的表达并没有很好的记录。免疫组化法检测手术标本中CD 47的表达。采用流式细胞术检测胃癌细胞系中CD 47和CD 44（一种已知的胃癌干细胞标志物）的表达。根据CD 44和CD 47表达水平，通过荧光激活细胞分选法分选MKN 45和MKN 74胃癌细胞，并研究其体外增殖、球体形成能力和体内致瘤性。在存在CD 47阻断性单克隆抗体（B6 H12）的情况下，将人巨噬细胞对癌细胞的体外吞噬作用以及腹腔内植入MKN 45细胞和B6 H12的免疫缺陷小鼠的存活率与使用对照抗体的实验进行比较。免疫组化结果显示，115例中57例CD 47阳性，CD 47阳性是独立的不良预后因素。大约90%的MKN 45和MKN 74细胞表达CD 47和CD 44。CD 47 hi细胞的体外增殖能力和球形集落形成能力均显著高于CD 47 lo细胞，CD 44 hiCD 47 hi细胞的体外增殖能力和体内致瘤性均显著高于CD 47 lo细胞。与对照抗体相比，B6 H12显著增强了人巨噬细胞对癌细胞的体外吞噬作用，并延长了小鼠腹膜内癌扩散的存活。结论：CD 47是胃癌的一个不良预后因子和有希望的治疗靶点。
CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47lo, and CD44hiCD47hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer.