Use of a SCID mouse model to select for a more aggressive strain of prostate cancer.
BACKGROUND
Prostate cancer is the most common non-cutaneous malignancy to affect men and has a propensity for metastasizing to bone. To better mimic the biology of metastatic prostate cancer, we have developed a model that utilizes both human prostate cancer and human bone in the SCID mouse.


METHODS
Injection of a xenograft of human prostate cancer, LAPC-4, near a human bone core that was previously implanted within the hindlimb of a SCID mouse allowed for the selection of a more aggressive subset of cells, known as LAPC-4(2) (read as "LAPC-4 squared").


RESULTS
As compared to LAPC-4 cells, these "bone-selected" LAPC-4(2) cells form tumors more rapidly, develop PSA-positive serum at an earlier time-point as well as with higher levels, develop androgen independence, and metastasize to human bone after orthotopic injection.


CONCLUSIONS
The selection of a more aggressive subset of prostate cancer cells that have developed androgen independence and the propensity to metastasize is of paramount importance as these are the cellular characteristics that are clinically linked to morbidity. Analysis of these "bone-selected" cells may lead to a better understanding of the molecular basis behind the conversion of low-grade prostate carcinoma to its more deadly, metastatic form.
Davies
Mark R
MR
Department of Orthopaedic Surgery, UCLA School of Medicine, Los Angeles, CA, USA.
Lee
Yu-Po
YP
Lee
Christopher
C
Zhang
Xuguang
X
Afar
Daniel E
DE
Lieberman
Jay R
JR
D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary; D016025:Bone Transplantation; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous