Wu T T, Sikes R A, Cui Q, Thalmann G N, Kao C, Murphy C F, Yang H, Zhau H E, Balian G, Chung L W
Department of Urology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Int J Cancer. 1998 Sep 11;77(6):887-94. doi: 10.1002/(sici)1097-0215(19980911)77:6<887::aid-ijc15>3.0.co;2-z.
LNCaP lineage-derived human prostate cancer cell lines C4-2 and C4-2B4 acquire androgen independence and osseous metastatic potential in vivo. Using C4-2 and C4-2B4 the goals of the current investigation were 1) to establish an ideal bone xenograft model for prostate cancer cells in intact athymic or SCID/bg mice using an intraosseous route of tumor cell administration and 2) to compare prostate cancer metastasis by administering cells either through intravenous (i.v.) or intracardiac administration in athymic or SCID/bg mice. Subsequent to tumor cell administration, prostate cancer growth in the skeleton was assessed by radiographic bone density, serum prostate-specific antigen (PSA) levels, presence of hematogenous prostate cancer cells and histopathologic evaluation of tumor specimens in the lymph node and skeleton. Our results show that whereas LNCaP cells injected intracardially failed to develop metastasis, C4-2 cells injected similarly had the highest metastatic capability in SCID/bg mice. Retroperitoneal and mediastinal lymph node metastases were noted in 3/7 animals, whereas 2/7 animals developed osteoblastic spine metastases. Intracardiac injection of C4-2 in athymic hosts produced spinal metastases in 1/5 animals at 8-12 weeks post-injection; PC-3 injected intracardially also metastasized to the bone but yielded osteolytic responses. Intravenous injection of either LNCaP or C4-2 failed to establish tumor colonies. Intrailiac injection of C4-2 but not LNCaP nor C4-2B4 cells in athymic mice established rapidly growing tumors in 4/8 animals at 2-7 weeks after inoculation. Intrafemoral injection of C4-2 (9/16) and C4-2B4 (5/18) but not LNCaP (0/13) cells resulted in the development of osteoblastic bone lesions in athymic mice (mean: 6 weeks, range: 3-12 weeks). In SCID/bg mice, intrafemoral injection of LNCaP (6/8), C4-2 (8/8) and C4-2B4 (8/8) cells formed PSA-producing, osteoblastic tumors in the bone marrow space within 3-5 weeks after tumor cell inoculation. A stepwise increase of serum PSA was detected in all animals. Reverse transcription-polymerase chain reaction (RT-PCR) to detect hematogenously disseminated prostate cancer cells could not be correlated to either serum PSA level or histological evidence of tumor cells in the marrow space. We have thus established a PSA-producing and osteoblastic human prostate cancer xenograft model in mice.
源自LNCaP谱系的人前列腺癌细胞系C4-2和C4-2B4在体内获得了雄激素非依赖性和骨转移潜能。利用C4-2和C4-2B4，本研究的目标是：1）通过肿瘤细胞骨内给药途径，在完整的无胸腺或SCID/bg小鼠中建立一种理想的前列腺癌细胞骨异种移植模型；2）在无胸腺或SCID/bg小鼠中，通过静脉内（i.v.）或心内给药来比较前列腺癌转移情况。在肿瘤细胞给药后，通过放射学骨密度、血清前列腺特异性抗原（PSA）水平、血行性前列腺癌细胞的存在以及肿瘤标本在淋巴结和骨骼中的组织病理学评估来评估前列腺癌在骨骼中的生长情况。我们的结果显示，心内注射LNCaP细胞未能发生转移，而同样进行心内注射的C4-2细胞在SCID/bg小鼠中具有最高的转移能力。在3/7的动物中发现了腹膜后和纵隔淋巴结转移，而2/7的动物出现了成骨性脊柱转移。在无胸腺宿主中的心内注射C4-2，在注射后8 - 12周时，1/5的动物发生了脊柱转移；心内注射PC-3也转移到了骨骼，但产生的是溶骨性反应。静脉注射LNCaP或C4-2均未能形成肿瘤集落。在无胸腺小鼠中，髂内注射C4-2而非LNCaP或C4-2B4细胞，在接种后2 - 7周时，4/8的动物中形成了快速生长的肿瘤。股内注射C4-2（9/16）和C4-2B4（5/18）而非LNCaP（0/13）细胞，导致无胸腺小鼠出现成骨性骨病变（平均：6周，范围：3 - 12周）。在SCID/bg小鼠中，股内注射LNCaP（6/8）、C4-2（8/8）和C4-2B4（8/8）细胞，在肿瘤细胞接种后3 - 5周内，在骨髓腔内形成了产生PSA的成骨性肿瘤。在所有动物中均检测到血清PSA的逐步升高。用于检测血行播散前列腺癌细胞的逆转录-聚合酶链反应（RT-PCR）结果与血清PSA水平或骨髓腔内肿瘤细胞的组织学证据均无相关性。因此，我们在小鼠中建立了一种产生PSA的成骨性人前列腺癌异种移植模型。
