Molecular Staging of Prostate-Bone Materials
Final rept. 1 Oct 1998-31 Mar 2001
SAINT VINCENT'S INST OF MEDICAL RESEARCH VICTORIA (AUSTRALIA)
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To molecularly define the different steps in prostate-bone metastasis, we developed a new human xenograft model for osteosclerotic bone metastasis after intracardiac inoculation in SCID mice. Individual clones of BAG-tagged C4-2 cells show a range of bone colonization capacities, however C4-2-3H5 generates overt osteosclerotic lesions after 4 months. Subcutaneous xenograft material from the 3H5-BAC, one other subline showing molecular metastases, and two sub-lines with very low bone-metastasising capabilities were subjected to gene array analysis and a series of candidate genes either up- or down-regulated have been identified. Intra-tibial inoculation of bones showed that each of these sub-lines has similar capacity to grow in bones, emphasizing bone homing extravasation events as being the cause of differential activity. Further funding is required for real-time quantitative PCR TaqMan of prostate biopsies and radical prostatectomies which have been accrued, and in situ hybridization andor immunohistochemistry analysis on tissue arrays. Continued attempts to refine the animal model and dissect the morphologic and molecular etiology of prostate bone metastasis have been limited by the low frequency of bone metastasis in this model, and the long latency period. Attempts to develop an alternative model using xenografted primary prostatic material have been initiated.
- Anatomy and Physiology
- Medicine and Medical Research