Sato N, Gleave M E, Bruchovsky N, Rennie P S, Beraldi E, Sullivan L D
Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, Canada.
Cancer Res. 1997 Apr 15;57(8):1584-9.
Several metastasizing murine and human animal models for prostate cancer are available. However, these models are androgen-independent and lack differentiated features such as androgen receptor and androgen-regulated gene expression like prostate-specific antigen (PSA). The objective of this study was to develop a metastasizing prostate cancer model with differentiated features using the human LNCaP cell line. Athymic and SCID mice were injected either s.c. or intraprostatically with 1 x 10(6) LNCaP cells. Changes in serum and tumor PSA mRNA levels were determined before and after castration to assess time to androgen-independent progression. Local tumor and metastatic growth was assessed at sacrifice after 12 weeks. Reverse transcription-PCR (RT-PCR) was used to detect circulating LNCaP cells. LNCaP tumor incidence after s.c. injection was 100% (65 of 65) in SCID mice and 80% in athymic mice. No lymph node or distant metastases were observed with s.c. tumors, and RT-PCR for PSA transcripts was negative. Primary tumor incidence after intraprostatic injection was 89% (39 of 44) in SCID mice and 60% in athymic mice. In 10 SCID mice with primary tumors followed for 12 weeks, retroperitoneal or mediastinal lymph node metastases were found in 100%, and microscopic pulmonary metastases were identified in 40%. RT-PCR for PSA transcripts was positive in 3 of 10 mice tested. Serum PSA levels in mice with s.c. and intraprostatic tumors decreased by 65% to nadir levels at 7 and 4 days after castration, respectively. Serum PSA and LNCaP tumor PSA mRNA levels increased to precastration levels earlier in SCID mice with intraprostatic tumors compared to those with s.c. tumors. Intraprostatic injection of LNCaP cells in SCID mice provides a useful animal model to investigate mechanisms of metastasis and to evaluate therapies targeted toward inhibiting the metastatic cascade.
目前已有多种用于前列腺癌的转移性小鼠和人类动物模型。然而，这些模型是雄激素非依赖性的，缺乏诸如雄激素受体和雄激素调节基因表达（如前列腺特异性抗原，PSA）等分化特征。本研究的目的是利用人LNCaP细胞系建立一个具有分化特征的转移性前列腺癌模型。将无胸腺小鼠和SCID小鼠皮下或前列腺内注射1×10⁶个LNCaP细胞。在去势前后测定血清和肿瘤PSA mRNA水平，以评估雄激素非依赖性进展的时间。12周后处死小鼠时评估局部肿瘤和转移生长情况。采用逆转录聚合酶链反应（RT-PCR）检测循环中的LNCaP细胞。皮下注射后，SCID小鼠的LNCaP肿瘤发生率为100%（65只中的65只），无胸腺小鼠为80%。皮下肿瘤未观察到淋巴结或远处转移，PSA转录本的RT-PCR检测为阴性。前列腺内注射后，SCID小鼠的原发性肿瘤发生率为89%（44只中的39只），无胸腺小鼠为60%。在10只随访12周的有原发性肿瘤的SCID小鼠中，100%发现腹膜后或纵隔淋巴结转移，40%发现微小肺转移。在10只检测的小鼠中有3只PSA转录本的RT-PCR检测呈阳性。皮下和前列腺内肿瘤小鼠的血清PSA水平分别在去势后7天和4天下降至最低点，下降了65%。与皮下肿瘤小鼠相比，前列腺内肿瘤的SCID小鼠血清PSA和LNCaP肿瘤PSA mRNA水平更早恢复到去势前水平。在SCID小鼠前列腺内注射LNCaP细胞提供了一个有用的动物模型，可用于研究转移机制和评估针对抑制转移级联反应的治疗方法。
