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 epithelial-mesenchymal 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.
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 epithelial-mesenchymal 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 cancerpatients 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 cancerpatients.
Authors: D T Chen; E R Weeks; J C Crocker; M F Islam; R Verma; J Gruber; A J Levine; T C Lubensky; A G Yodh Journal: Phys Rev Lett Date: 2003-03-14 Impact factor: 9.161
Authors: Thomas Dittmar; Christoph Heyder; Eva Gloria-Maercker; Wolfgang Hatzmann; Kurt S Zänker Journal: Clin Exp Metastasis Date: 2007-09-08 Impact factor: 5.150
Authors: Howard I Scher; Xiaoyu Jia; Johann S de Bono; Martin Fleisher; Kenneth J Pienta; Derek Raghavan; Glenn Heller Journal: Lancet Oncol Date: 2009-02-11 Impact factor: 41.316
Authors: Johann S de Bono; Howard I Scher; R Bruce Montgomery; Christopher Parker; M Craig Miller; Henk Tissing; Gerald V Doyle; Leon W W M Terstappen; Kenneth J Pienta; Derek Raghavan Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Mark Jesus M Magbanua; Hope S Rugo; Denise M Wolf; Louai Hauranieh; Ritu Roy; Praveen Pendyala; Eduardo V Sosa; Janet H Scott; Jin Sun Lee; Brandelyn Pitcher; Terry Hyslop; William T Barry; Steven J Isakoff; Maura Dickler; Laura Van't Veer; John W Park Journal: Clin Cancer Res Date: 2018-01-08 Impact factor: 12.531
Authors: Ronald Rodriguez; Shawn E Lupold; Ping Wu; Lori J Sokoll; Tarana A Kudrolli; Wasim H Chowdhury; Rong Ma; Minzhi M Liu Journal: Prostate Date: 2014-07-25 Impact factor: 4.104
Authors: Jie Mu; Xuguang Tai; Shankar S Iyer; Jocelyn D Weissman; Alfred Singer; Dinah S Singer Journal: J Immunol Date: 2014-02-12 Impact factor: 5.422
Authors: Giuseppe Galletti; Luigi Portella; Scott T Tagawa; Brian J Kirby; Paraskevi Giannakakou; David M Nanus Journal: Mol Diagn Ther Date: 2014-08 Impact factor: 4.074
Authors: Ya-Ting Hsu; Pawel Osmulski; Yao Wang; Yi-Wen Huang; Lu Liu; Jianhua Ruan; Victor X Jin; Nameer B Kirma; Maria E Gaczynska; Tim Hui-Ming Huang Journal: Cancer Res Date: 2016-08-28 Impact factor: 12.701