Development of an animal model for prostate cancer cell metastasis to adult human bone

Background. Prostate cancer metastases to bone are associated with signific ant morbidity and mortality. Presently, there is little known about the bio logical interaction between prostate cancer cells and bone. Development of an animal model using adult human bone will enhance our ability to study th e biology of prostate cancer metastasis to bone. Methods. Bone was harveste d from patients undergoing total joint arthroplasty and implanted in the hi ndlimbs of pre-treated SCID mice. Two months after bone implantation 4 X 10 4 prostate cancer cells (PC-3 ol LAPC-4) were injected near the bone implan tation site. The animals were sacrificed approximately 8 to 12 weeks after the injections of the cells. Complete histological analysis including immun ostaining was performed Results. Both the PC-3 and LAPC-4 prostate cancer c ells homed to the human bone implant, specifically the reconstituted bone m arrow cavity. Analysis of the bone-tumor interaction after injection of PC- 3 cells revealed strong labeling for PTHrP, TNF alpha and IL-6, consistent with osteoclast recruitment and osteoclast activity These cells also were p ositively stained for CK18. After cellular injection of LAPC-4 cells, there was shang labeling for TNFa, IL-6, and IL-I (osteoclast recruitment and os teolytic activity). PTHrP staining was also noted. The bone cells were stro ngly stained for osteocalcin, and the tumor cells for PSA. Conclusions. The se data suggest that the tumor cells may induce an osteolytic response to e nhance their ability to metastasize to bone. This animal model allows us to study the biologic interaction between prostate cancer cells and human bon e and may enhance our understanding of the events associated with prostate cancer metastasis to bone.