Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma.
Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma.
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血管紧张素转换酶2是EGFR突变肺腺癌的潜在治疗靶点。
DOI：
10.1016/j.bbrc.2017.04.102
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发表时间：
2017-06-03
影响因子：
3.1
通讯作者：
Sakuma Y
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Hirai S;Sumi T;Tanaka Y;Tada M;Nishii Y;Hasegawa T;Uchida H;Yamada G;Watanabe A;Takahashi H;Sakuma Y
EGFR 突变型肺腺癌含有经历上皮间质转化的细胞亚群，并且可以独立于 EGFR 生长。为了杀死这些癌细胞，我们需要 EGFR 抑制剂以外的新治疗方法。如果一种分子在这种不依赖EGFR的EGFR突变癌细胞的细胞表面上特异性表达，则它可以成为治疗靶点。我们发现，源自 HCC827 细胞（一种 EGFR 突变型肺腺癌细胞系）的间充质 EGFR 独立亚系比其亲代细胞更能表达血管紧张素转换酶 2 (ACE2)。 ACE2在大多数检测的原发性EGFR突变肺腺癌中也至少部分表达，并且癌细胞中ACE2的表达水平远高于正常肺上皮细胞。此外，我们还开发了一种抗 ACE2 小鼠单克隆抗体 (mAb)，称为 H8R64，可被表达 ACE2 的细胞内化。如果生产出由基于H8R64的人源化单克隆抗体和强效抗癌药物组成的抗体-药物缀合物，可能会有效治疗EGFR突变型肺腺癌。间充质 EGFR 突变肺腺癌细胞系表达 ACE2。 EGFR 突变的肺腺癌组织含有表达 ACE2 的癌细胞。我们开发了一种可被 ACE2 阳性细胞内化的抗 ACE2 抗体。 ACE2是EGFR突变肺癌的潜在治疗靶点。
EGFR-mutant lung adenocarcinomas contain a subpopulation of cells that have undergone epithelial-to-mesenchymal transition and can grow independently of EGFR. To kill these cancer cells, we need a novel therapeutic approach other than EGFR inhibitors. If a molecule is specifically expressed on the cell surface of such EGFR-independent EGFR-mutant cancer cells, it can be a therapeutic target. We found that a mesenchymal EGFR-independent subline derived from HCC827 cells, an EGFR-mutant lung adenocarcinoma cell line, expressed angiotensin-converting enzyme 2 (ACE2) to a greater extent than its parental cells. ACE2 was also expressed at least partially in most of the primary EGFR-mutant lung adenocarcinomas examined, and the ACE2 expression level in the cancer cells was much higher than that in normal lung epithelial cells. In addition, we developed an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized mAb based on H8R64 and a potent anticancer drug were produced, it could be effective for the treatment of EGFR-mutant lung adenocarcinomas. A mesenchymal EGFR-mutant lung adenocarcinoma cell line expresses ACE2. EGFR-mutant lung adenocarcinoma tissues contain cancer cells that express ACE2. We developed an anti-ACE2 antibody that is internalized by ACE2-positive cells. ACE2 is a potential therapeutic target for EGFR-mutant lung cancer.
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血管紧张素转换酶 2 可预防致命的甲型禽流感 H5N1 感染
影响因子：
16.6
作者：
Zou Z;Yan Y;Shu Y;Gao R;Sun Y;Li X;Ju X;Liang Z;Liu Q;Zhao Y;Guo F;Bai T;Han Z;Zhu J;Zhou H;Huang F;Li C;Lu H;Li N;Li D;Jin N;Penninger JM;Jiang C
通讯作者：
Jiang C
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
5.2
作者：
Nishii, Yukari;Yamaguchi, Miki;Sakuma, Yuji
通讯作者：
Sakuma, Yuji
影响因子：
17.1
作者：
Sequist LV;Waltman BA;Dias-Santagata D;Digumarthy S;Turke AB;Fidias P;Bergethon K;Shaw AT;Gettinger S;Cosper AK;Akhavanfard S;Heist RS;Temel J;Christensen JG;Wain JC;Lynch TJ;Vernovsky K;Mark EJ;Lanuti M;Iafrate AJ;Mino-Kenudson M;Engelman JA
通讯作者：
Engelman JA