Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer
Article first published online: 31 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 73, Issue 8, pages 813–826, June 2013
How to Cite
Chen, C.-L., Mahalingam, D., Osmulski, P., Jadhav, R. R., Wang, C.-M., Leach, R. J., Chang, T.-C., Weitman, S. D., Kumar, A. P., Sun, L., Gaczynska, M. E., Thompson, I. M. and Huang, T. H.-M. (2013), Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate, 73: 813–826. doi: 10.1002/pros.22625
- Issue published online: 25 APR 2013
- Article first published online: 31 DEC 2012
- Manuscript Accepted: 2 NOV 2012
- Manuscript Received: 21 AUG 2012
- Integrative Cancer Biology Program. Grant Number: U54CA113001
- Early Detection Research Network. Grant Number: U01CA086402
- Cancer Center Support Grant. Grant Number: P30CA054174
- prostate cancer;
- circulating tumor cells;
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 epithelial–mesenchymal transition (EMT) are strong predictors of metastatic prostate cancer.
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.
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.
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: 813–826, 2013. © 2012 Wiley Periodicals, Inc.