Deciphering the cellular source of tumor relapse identifies CD44 as a major therapeutic target in pancreatic adenocarcinoma.
Deciphering the cellular source of tumor relapse identifies CD44 as a major therapeutic target in pancreatic adenocarcinoma.
复制标题
肿瘤复发的细胞来源破译将CD44鉴定为胰腺腺癌的主要治疗靶点。
DOI：
10.18632/oncotarget.3510
复制
发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Iovanna J
中科院分区：
文献类型：
--
作者：
Molejon MI;Tellechea JI;Loncle C;Gayet O;Gilabert M;Duconseil P;Lopez-Millan MB;Moutardier V;Gasmi M;Garcia S;Turrini O;Ouaissi M;Poizat F;Dusetti N;Iovanna J
在胰导管腺癌（Pancreatic Ductal Adenocarcinoma， PDAC）患者中，经过一段时间对标准治疗的满意反应后，肿瘤变得无反应，患者很快死亡。这种现象主要是由于残余肿瘤的快速和不受控制的发展。PDAC中残留肿瘤细胞的起源和生物学特性尚不清楚。在这项工作中，我们使用了保存在裸鼠体内的PDAC作为异种移植物，证明了残留的PDAC肿瘤起源于肿瘤中存在的少量CD44+细胞。在PDAC复发期间，增殖的CD44+细胞降低ZEB1的表达，同时过表达MUC1蛋白，并获得分化的形态学和生物学特征。此外，我们报告了原发性和残余PDAC肿瘤中的CD44+细胞是异质群体的一部分，其中包括不同数量的CD133+和EpCAM+细胞。我们在标准PDAC治疗后的人类复发病例样本中证实了CD44+细胞的增殖。最后，通过体内系统给药抗CD44抗体，我们证明了CD44是治疗肿瘤复发的有效治疗靶点，但不是原发性PDAC肿瘤。我们得出结论，CD44+细胞产生复发性肿瘤，因此，它们本身是治疗复发性PDAC患者的有希望的治疗靶点。
It has been commonly found that in patients presenting Pancreatic Ductal Adenocarcinoma (PDAC), after a period of satisfactory response to standard treatments, the tumor becomes non-responsive and patient death quickly follows. This phenomenon is mainly due to the rapid and uncontrolled development of the residual tumor. The origin and biological characteristics of residual tumor cells in PDAC still remain unclear. In this work, using PDACs from patients, preserved as xenografts in nude mice, we demonstrated that a residual PDAC tumor originated from a small number of CD44+ cells present in the tumor. During PDAC relapse, proliferating CD44+ cells decrease expression of ZEB1, while overexpressing the MUC1 protein, and gain morphological and biological characteristics of differentiation. Also, we report that CD44+ cells, in primary and residual PDAC tumors, are part of a heterogeneous population, which includes variable numbers of CD133+ and EpCAM+ cells. We confirmed the propagation of CD44+ cells in samples from cases of human relapse, following standard PDAC treatment. Finally, using systemic administration of anti-CD44 antibodies in vivo, we demonstrated that CD44 is an efficient therapeutic target for treating tumor relapse, but not primary PDAC tumors. We conclude that CD44+ cells generate the relapsing tumor and, as such, are themselves promising therapeutic targets for treating patients with recurrent PDAC.
登录
查看更多内容
影响因子：
9.7
作者：
Malaney, Prerna;Nicosia, Santo V.;Dave, Vrushank
通讯作者：
Dave, Vrushank
影响因子：
9.7
作者：
Hung, Sau Wai;Mody, Hardik R.;Govindarajan, Rajgopal
通讯作者：
Govindarajan, Rajgopal
影响因子：
29.4
作者：
Li L;Hao X;Qin J;Tang W;He F;Smith A;Zhang M;Simeone DM;Qiao XT;Chen ZN;Lawrence TS;Xu L
通讯作者：
Xu L
影响因子：
24.5
作者：
Neesse, Albrecht;Michl, Patrick;Tuveson, David A.
通讯作者：
Tuveson, David A.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.