A novel, spontaneously immortalized, human prostate cancer cell line, Bob, offers a unique model for pre-clinical prostate cancer studies.
BACKGROUND
New in vitro models of castration-resistant prostate cancer (CRPC) are urgently required.


METHODS
Trans-rectal needle biopsies (TRBP) of the prostate were performed for research purposes on progressing CRPC patients who had not received prior treatment to the prostate. Biopsies were immediately digested with collagenase and plated onto collagen-coated flasks with a feeder layer of 3T6 cells and cultured in cytokine-supplemented keratinocyte serum-free medium.


RESULTS
Biopsies from 25 patients were collected and one of these, following an initial period of crisis, spontaneously immortalized. A series of cell lines called Bob were then established from a clone that survived CD133-selection followed by 4 weeks under adhesion-independent conditions in methylcellulose. Gains and losses previously described in clinical prostate tumors, most notably loss of 8(p) and gain of 8(q), were identified on comparative genomic hybridization and long-term growth in culture, survival in methylcellulose and invasion through matrigel confirmed the malignant phenotype of Bob. Furthermore, Bob expressed high levels of p53 and markers of early differentiation, including K8, prostatic acid phosphatase and prostate stem cell antigen. There was, however, no in vivo growth and ERG and ETV1 were not rearranged. Growth in serum permitted some differentiation.


CONCLUSIONS
This is the first spontaneously immortalized prostate cancer cell line to be established from a TRBP of a patient with CRPC. Bob is a novel pre-clinical model for functional studies in CRPC and especially for studying the CRPC "basal" phenotype.
Attard
Gerhardt
G
The Institute of Cancer Research, Surrey, UK.
Rizzo
Sian
S
Ledaki
Ioanna
I
Clark
Jeremy
J
Reid
Alison H M
AH
Thompson
Alan
A
Khoo
Vincent
V
de Bono
Johann S
JS
Cooper
Colin S
CS
Hudson
David L
DL
D000818:Animals; D001707:Biopsy, Needle; D001798:Blood Proteins / Q000494:pharmacology; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation / Q000379:methods*; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000032:analysis; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008297:Male; D008747:Methylcellulose; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D018874:Spheroids, Cellular
D001798:Blood Proteins; D004273:DNA, Neoplasm; C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D008747:Methylcellulose