Glioblastoma stem cells exploit the αvβ8 integrin-TGFβ1 signaling axis to drive tumor initiation and progression

被引：46

作者：

Guerrero, P. A. ^{[1
]}

Tchaicha, J. H. ^{[1
]}

Chen, Z. ^{[1
]}

Morales, J. E. ^{[1
]}

McCarty, N. ^{[2
]}

Wang, Q. ^{[3
,4
]}

Sulman, E. P. ^{[3
,4
,5
]}

Fuller, G. ^{[6
]}

Lang, F. F. ^{[1
]}

Rao, G. ^{[1
]}

McCarty, J. H. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, 1515 Holcombe Blvd,Unit 1004, Houston, TX 77030 USA

[2] Univ Texas Hlth Sci Ctr Houston, Brown Inst Mol Med, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

来源：

ONCOGENE | 2017年 / 36卷 / 47期

关键词：

GROWTH-FACTOR-BETA; ANTI-VEGF THERAPY; TGF-BETA; INTEGRIN ALPHA-V-BETA-8; ANTIANGIOGENIC THERAPY; CEREBRAL-HEMORRHAGE; SELF-RENEWAL; BRAIN; CANCER; EXPRESSION;

D O I：

10.1038/onc.2017.248

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin alpha v beta 8 and its latent transforming growth factor beta 1 (TGF beta 1) protein ligand have central roles in promoting niche co-option and GBM initiation. alpha v beta 8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of beta 8(high) cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that alpha v beta 8 integrin regulates tumor development, in part, by driving TGF beta 1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the av beta 8 integrin-TGF beta 1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.

引用

页码：6568 / 6580

页数：13

共 69 条

[1] Endothelial Expression of TGFβ Type II Receptor Is Required to Maintain Vascular Integrity during Postnatal Development of the Central Nervous System [J].