Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer

被引：185

作者：

Chen, Chun-Liang ^{[1
]}

Mahalingam, Devalingam ^{[2
]}

Osmulski, Pawel ^{[1
]}

Jadhav, Rohit R. ^{[1
]}

Wang, Chiou-Miin ^{[1
]}

Leach, Robin J. ^{[3
,4
]}

Chang, Tien-Cheng ^{[5
]}

Weitman, Steven D. ^{[6
,7
]}

Kumar, Addanki Pratap ^{[4
]}

Sun, LuZhe ^{[3
]}

Gaczynska, Maria E. ^{[1
]}

Thompson, Ian M. ^{[4
]}

Huang, Tim Hui-Ming ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Dept Mol Med, San Antonio, TX 78229 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[5] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[7] Univ Texas Hlth Sci Ctr San Antonio, Dept Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

来源：

PROSTATE | 2013年 / 73卷 / 08期

基金：

美国国家卫生研究院;

关键词：

prostate cancer; circulating tumor cells; metastasis; EPITHELIAL-MESENCHYMAL TRANSITION; ANDROGEN RECEPTOR; STEM-CELLS; BIOMARKERS; SURVIVAL; PREDICT; PCR;

D O I：

10.1002/pros.22625

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND Prostate tumors shed circulating tumor cells (CTCs) into the blood stream. Increased evidence shows that CTCs are often present in metastatic prostate cancer and can be alternative sources for disease profiling and prognostication. Here we postulate that CTCs expressing genes related to epithelialmesenchymal transition (EMT) are strong predictors of metastatic prostate cancer. METHODS A microfiltration system was used to trap CTCs from peripheral blood based on size selection of large epithelial-like cells without CD45 leukocyte marker. These cells individually retrieved with a micromanipulator device were assessed for cell membrane physical properties using atomic force microscopy. Additionally, 38 CTCs from eight prostate cancer patients were used to determine expression profiles of 84 EMT-related and reference genes using a microfluidics-based PCR system. RESULTS Increased cell elasticity and membrane smoothness were found in CTCs compared to noncancerous cells, highlighting their potential invasiveness and mobility in the peripheral circulation. Despite heterogeneous expression patterns of individual CTCs, genes that promote mesenchymal transitioning into a more malignant state, including IGF1, IGF2, EGFR, FOXP3, and TGFB3, were commonly observed in these cells. An additional subset of EMT-related genes (e.g., PTPRN2, ALDH1, ESR2, and WNT5A) were expressed in CTCs of castration-resistant cancer, but less frequently in castration-sensitive cancer. CONCLUSIONS The study suggests that an incremental expression of EMT-related genes in CTCs is associated with metastatic castration-resistant cancer. Although CTCs represent a group of highly heterogeneous cells, their unique EMT-related gene signatures provide a new opportunity for personalized treatments with targeted inhibitors in advanced prostate cancer patients. Prostate 73: 813826, 2013. (c) 2012 Wiley Periodicals, Inc.

引用

页码：813 / 826

页数：14

共 38 条

[1]

Models, mechanisms and clinical evidence for cancer dormancy [J].