Presentation Abstract

Abstract Number: 804
Presentation Title: Disseminated tumor cell heterogeneity and dormancy in prostate cancer
Presentation Time: Sunday, Apr 07, 2013, 1:00 PM - 5:00 PM
Location: Hall A-E, Poster Section 34
Poster Board Number: 11
Author Block: Hung-Ming Lam1, Lisly Chéry1, Ilsa Coleman2, Bryce Lakely1, Sandy Larson1, Roger Coleman2, Lisha Brown1, Kathy Doan1, Jennifer Noteboom1, Xiaotun Zhang1, Lawrence True1, Peter Nelson2, Bruce Montgomery1, Paul Lange1, Linda Snyder3, Robert Vessella1, Colm Morrissey1. 1University of Washington, Seattle, WA; 2Fred Hutchinson Cancer Center, Seattle, WA; 3Janssen Research and Development, Radnor, PA
Abstract Body: Prostate cancer (PCa) can remain in the bone marrow for a prolonged period of time (>5 years) while the patient shows no evidence of disease before the cancer eventually recurs. Dormant cancer cells can be detected in bone, the principal metastatic site of PCa, and these bone-homing cancer cells are known as disseminated tumor cells (DTC). Little information is available on the heterogeneity and dormancy of DTC in PCa. In this study, we isolated and compared the gene expression profile of individual DTC (n=45) from the bone marrow of 4 PCa patients with no evidence of disease and 5 patients with advanced disease. Using principle component analysis and cluster analysis of the 1000 most variable genes, we determined the heterogeneity of the DTC population within each patient. To identify a dormancy signature from DTC in the bone marrow and primary PCa cells, we carried out two gene expression analyses: DTC in patients with no evidence of disease vs. those with advanced disease, and primary PCa tissues from patients with a short vs. long dormancy period post radical prostatectomy (8-86 months). Genes associated in other cancers with cellular senescence, cell-cycle inhibition, and dormancy were analyzed. Candidate genes from both gene expression arrays were validated at the protein level by a tissue microarray consisting of 64 primary PCa cases that recurred after either a short or long dormancy period post radical prostatectomy (6-121 months).
The identification of heterogeneous gene signatures in DTC and novel proteins that promote dormancy will guide the development of possible biomarkers and therapeutic targets to prevent PCa recurrence, possibly by either eliminating DTC or inhibiting their escape from dormancy.