Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropi sm of PC cells for bone, we engrafted humanized non-obese diabetic/severe c ombined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 tells h ad metastasized specifically to HAB in 35 and 65%, respectively, of the mic e. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding os teogenic response. A feature of experimental metastasis of PC in NOD/SCID-h u mice was its specificity for HAB tissue. Human PC cells had no or very lo w metastatic potential in regard to implanted HAL, mouse hone, or native mo use hone, These findings indicate that metastasis of PC cells to HAB is bot h species and tissue specific, The availability of this small animal model could provide a useful tool for identifying and analyzing important feature s of the human PC metastatic process that cannot he addressed in convention al metastasis models.