Mp90-13 circulating tumor cells-derived patient xenografts: a novel approach to study prostate cancer lethal progression

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-13 CIRCULATING TUMOR CELLS-DERIVED PATIENT XENOGRAFTS: A NOVEL APPROACH TO STUDY PROSTATE CANCER LETHAL PROGRESSION Gina C.Y. Chu, Ruoxiang Wang, Haiyen E. Zhau, Edwin M. Posadas, and Leland W.K. Chung Gina C.Y. ChuGina C.Y. Chu More articles by this author , Ruoxiang WangRuoxiang Wang More articles by this author , Haiyen E. ZhauHaiyen E. Zhau More articles by this author , Edwin M. PosadasEdwin M. Posadas More articles by this author , and Leland W.K. ChungLeland W.K. Chung More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2557AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Circulating tumor cells (CTCs) from patient’s blood represent a promising non-invasive liquid biopsy useful for cancer prognosis and diagnosis. Since CTCs reflect the pool of tumor cells originated from the primary and metastatic sites, molecular and phenotypic characterizations of CTCs allow us to understand the biology and metastatic process in prostate cancer (PC) patients. The major challenge of CTC research is the limited number of PC cells in blood making it difficult to repeat molecular and phenotypic assays, and validate in vitro results with patients’ clinical outcome. We established a novel in vitro CTC expansion protocol and patient-derived xenografts from CTCs (CTC-PDXs), evaluated gene expression and behavioral profiles of CTCs, and correlated these results with the clinical status of PC patients. METHODS Post-RBC lysed peripheral blood mononuclear cells (PBMCs) were used to expand CTCs. CTC-PDXs models were used to assess the growth, tumor formation and metastases in mice and results were correlated with the clinical status of the patients. Genetically tagged CTCs with GFP, RFP or Luc were used to detect local tumor growth and distant dissemination in mice. Gene expression was assayed by microarray, qRT-PCR, and western blot and cell behaviors determined by migration, invasion and anchorage-independent 3-D growth. RESULTS CTC-PDX models were established in mice from PBMCs collected from 8 PC patients. CTCs and CTC-PDXs were found to express variable levels of epithelial and PC-associated biomarkers (EpCAM, AR, PSA and PSMA). CTC-PDXs established from PBMCs collected longitudinally from post-therapy patients showed increased tumor growth, invasiveness, metastasis and caused earlier mouse death than those of the prior-therapy PBMCs. Metastasis-initiating cells (MICs, see Chu et al. Endocrene-related Cancer 21: 311, 2014) were identified in CTCs overexpressing genes associated with mesenchymal-, stem-, and neuroendocrine-cells. CTCs with MIC phenotype, remarkably recruit and re-program non-tumorigenic PC cells from primary tissues to express MIC phenotype and gain tumorigenic and bone colonizing capability. CONCLUSIONS Novel methods expanding CTCs in culture and CTC-PDX models in mice are established. CTCs with MIC phenotype are identified and shown to promote tumorigenic and metastatic behaviors in non-tumorigenic PC cells. MICs may be novel diagnostic, prognostic and therapeutic targets. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1149 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Gina C.Y. Chu More articles by this author Ruoxiang Wang More articles by this author Haiyen E. Zhau More articles by this author Edwin M. Posadas More articles by this author Leland W.K. Chung More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...