TGF-β Receptor Inhibitors Target the CD44high/Id1high Glioma-Initiating Cell Population in Human Glioblastoma

被引：532

作者：

Anido, Judit ^{[1
]}

Saez-Borderias, Andrea ^{[1
]}

Gonzalez-Junca, Alba ^{[1
]}

Rodon, Laura ^{[1
]}

Folch, Gerard ^{[1
]}

Carmona, Maria A. ^{[1
]}

Prieto-Sanchez, Rosa M. ^{[1
]}

Barba, Ignasi ^{[2
]}

Martinez-Saez, Elena ^{[3
]}

Prudkin, Ludmila ^{[1
]}

Cuartas, Isabel ^{[1
]}

Raventos, Carolina ^{[1
]}

Martinez-Ricarte, Francisco ^{[4
]}

Antonia Poca, M. ^{[4
]}

Garcia-Dorado, David ^{[2
]}

Lahn, Michael M. ^{[5
]}

Yingling, Jonathan M. ^{[5
]}

Rodon, Jordi ^{[1
]}

Sahuquillo, Juan ^{[4
,6
]}

Baselga, Jose ^{[1
,6
]}

Seoane, Joan ^{[1
,6
,7
]}

机构：

[1] Vall dHebron Inst Oncol, Barcelona 08035, Spain

[2] Vall dHebron Univ Hosp Res Inst, Cardiovasc Program, Barcelona 08035, Spain

[3] Vall dHebron Univ Hosp Res Inst, Pathol Program, Barcelona 08035, Spain

[4] Vall dHebron Univ Hosp Res Inst, Dept Neurosurg, Barcelona 08035, Spain

[5] Eli Lilly & Co, Indianapolis, IN 46225 USA

[6] Autonomous Univ Barcelona, Cerdanyola Del Valles 08193, Spain

[7] ICREA, Barcelona 08010, Spain

来源：

CANCER CELL | 2010年 / 18卷 / 06期

基金：

欧洲研究理事会;

关键词：

CANCER STEM-CELLS; LUNG METASTASIS; SELF-RENEWAL; SMAD; TUMORS; GENE; DIFFERENTIATION; ACTIVATION; EXPRESSION; INDUCTION;

D O I：

10.1016/j.ccr.2010.10.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF-beta inhibitors, currently under clinical development, target the GIG compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF-beta inhibition, which include inhibitors of DNA-binding protein (Id)-1 and -3 transcription factors. We have identified a cell population enriched for GICs that expresses high levels of CD44 and Id1 and tend to be located in a perivascular niche. The inhibition of the TGF-beta pathway decreases the CD44(high)/Id1(high) GIG population through the repression of Id1 and Id3 levels, therefore inhibiting the capacity of cells to initiate tumors. High CD44 and Id1 levels confer poor prognosis in GBM patients.

引用

页码：655 / 668

页数：14

共 35 条

[1]

[Anonymous], J CLIN ONCOL

[2]

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].