CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis.
CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis.
复制标题
CD47通过抑制巨噬细胞吞噬作用促进卵巢癌进展
DOI：
10.18632/oncotarget.16547
复制
发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Yao Z
中科院分区：
文献类型：
--
作者：
Liu R;Wei H;Gao P;Yu H;Wang K;Fu Z;Ju B;Zhao M;Dong S;Li Z;He Y;Huang Y;Yao Z
靶向CD 47有效地增强生理和病理条件下的巨噬细胞吞噬作用。抗CD 47抗体已显示出抑制几种类型的癌症的进展。然而，抗CD 47单克隆抗体（mAb）治疗的机制仍然存在争议。本研究证实CD 47蛋白在卵巢癌中高表达，并与卵巢癌的临床特征和预后不良相关。卵巢癌细胞系SK-OV-3中的CD 47敲低促进了体外巨噬细胞的吞噬作用，并抑制了体内肿瘤生长。这些数据表明，CD 47抑制是一种潜在的癌症治疗策略。使用抗CD 47 mAb，我们发现SK-0 V-3细胞和原代癌细胞中的CD 47抑制能够概括我们的敲除结果，并导致浸润巨噬细胞数量的增加。此外，CD 133+肿瘤起始细胞表达高水平的CD 47，抗CD 47 mAb处理能够触发该细胞群的吞噬作用。总之，我们的结果表明，CD 47抑制卵巢癌细胞的巨噬细胞吞噬功能，下调CD 47或用mAb抑制CD 47能够逆转这种负面作用。因此，CD 47抗体治疗可能是治疗卵巢癌的一种有前途的策略。
Targeting CD47 efficiently enhances macrophage phagocytosis in both physiological and pathological conditions. Anti-CD47 antibodies have been shown to inhibit the progression of several types of cancer. However, the mechanism of anti-CD47 monoclonal antibody (mAb) treatment remains controversial. In this study, we confirmed that CD47 protein is highly expressed in ovarian cancer, and is correlated with poor clinical characteristics and prognosis. CD47 knockdown in the ovarian cancer cell line, SK-OV-3, promoted phagocytosis by macrophages in vitro and inhibited tumor growth in vivo. These data combined suggest that CD47 inhibition is a potential strategy for cancer treatment. Using an anti-CD47 mAb, we found that CD47 inhibition in both SK-OV-3 cells and primary cancer cells was able to recapitulate our knockdown results and led to an increase in the number of infiltrating macrophages. In addition, the CD133+ tumor initiating cells expressed a high level of CD47, and anti-CD47 mAb treatment was able to trigger the phagocytosis of this cell population. In conclusion, our results indicate that CD47 inhibits macrophage phagocytosis of ovarian cancer cells, and down-regulation of CD47 or inhibiting CD47 by mAb was able to reverse the negative effect. Thus, CD47 antibody therapy may be a promising strategy to treat ovarian cancer.
登录
查看更多内容
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
影响因子：
3.7
作者：
Liu J;Wang L;Zhao F;Tseng S;Narayanan C;Shura L;Willingham S;Howard M;Prohaska S;Volkmer J;Chao M;Weissman IL;Majeti R
通讯作者：
Majeti R
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
来自原发性人类肿瘤的卵巢癌起始细胞的鉴定和表征
影响因子：
11.2
作者：
Zhang, Shu;Balch, Curt;Nephew, Kenneth P.
通讯作者：
Nephew, Kenneth P.