Tumour angiogenesis regulation by the miR-200 family

被引：366

作者：

Pecot, Chad V. ^{[1
]}

Rupaimoole, Rajesha ^{[2
]}

Yang, Da ^{[3
]}

Akbani, Rehan ^{[4
]}

Ivan, Cristina ^{[2
,5
]}

Lu, Chunhua ^{[2
]}

Wu, Sherry ^{[2
]}

Han, Hee-Dong ^{[2
]}

Shah, Maitri Y. ^{[6
]}

Rodriguez-Aguayo, Cristian ^{[6
]}

Bottsford-Miller, Justin ^{[2
]}

Liu, Yuexin

Kim, Sang Bae ^{[7
]}

Unruh, Anna ^{[4
]}

Gonzalez-Villasana, Vianey ^{[6
]}

Huang, Li ^{[8
]}

Zand, Behrouz ^{[2
]}

Moreno-Smith, Myrthala ^{[2
]}

Mangala, Lingegowda S. ^{[2
,5
]}

Taylor, Morgan ^{[2
]}

Dalton, Heather J. ^{[2
]}

Sehgal, Vasudha ^{[7
]}

Wen, Yunfei ^{[2
]}

Kang, Yu ^{[2
]}

Baggerly, Keith A. ^{[4
]}

Lee, Ju-Seog ^{[7
]}

Ram, Prahlad T. ^{[7
]}

Ravoori, Murali K. ^{[9
]}

Kundra, Vikas ^{[9
]}

Zhang, Xinna ^{[5
,8
]}

Ali-Fehmi, Rouba ^{[10
]}

Gonzalez-Angulo, Ana-Maria ^{[7
,11
]}

Massion, Pierre P. ^{[12
]}

Calin, George A. ^{[5
,6
]}

Lopez-Berestein, Gabriel ^{[5
,6
,8
]}

Zhang, Wei ^{[5
]}

Sood, Anil K. ^{[2
,5
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

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

[4] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA

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

[7] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA

[10] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Pathol, Detroit, MI 48201 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Breast Oncol, Houston, TX 77030 USA

[12] Vanderbilt Ingram Canc Ctr & Vet Affairs, Div Allergy Pulm & Crit Care Med, Thorac Program, Nashville, TN 37232 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; MICRORNA EXPRESSION PROFILES; SMALL INTERFERING RNA; LUNG-CANCER; REPRESSORS ZEB1; CELLS; GROWTH; CHEMORESISTANCE; CHEMOTHERAPY; METASTASIS;

D O I：

10.1038/ncomms3427

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent.

引用

页数：14

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