Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23.

Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23.
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发表时间:
1996-06
期刊:
Clinical cancer research : an official journal of the American Association for Cancer Research
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通讯作者:
W. Ellis;R. Vessella;K. Buhler;F. Bladou;L. True;S. Bigler;D. Curtis;P. Lange
W. Ellis;R. Vessella;K. Buhler;F. Bladou;L. True;S. Bigler;D. Curtis;P. Lange
中科院分区:
其他
文献类型:
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作者:
W. Ellis;R. Vessella;K. Buhler;F. Bladou;L. True;S. Bigler;D. Curtis;P. Lange

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前列腺癌已被证明极难建立细胞系或异种移植。在这篇文章中,我们描述了在胸腺小鼠中增殖的一系列新的前列腺癌异种移植物,命名为LuCaP 23,从死亡后不久的尸检中收集的前列腺转移瘤中发展而来。来自三个独立转移沉积物的肿瘤发展成三个异种移植亚群:两个来自淋巴结转移(LuCaP 23.1和23.8),一个来自肝脏转移(LuCaP 23.12)。荧光原位杂交分析证实异种移植物是人类。组织学上,异种移植物由排列成腺状的柱状上皮细胞组成。三种药物的肿瘤倍增时间从11天到21天不等。携带LuCaP 23.1、23.8和23.12亚系的小鼠细胞分泌大量的前列腺特异性抗原(PSA), PSA指数分别为1.27、1.63和5.21 ng/ml/mm3。在大多数肿瘤中,雄激素剥夺后,PSA分泌暂时减少,肿瘤大小减小。最终,肿瘤不再依赖雄激素,并在被阉割的宿主体内恢复生长。PSA对去势的反应程度和到达PSA最低点的时间与进展时间相关。因此,与大多数现有的前列腺癌模型不同,这种新型异种移植物表现出许多临床前列腺癌的表型特征,包括雄激素敏感性。这些特性使这种异种移植物成为未来研究的一个很好的模型。
Prostatic carcinoma has proven extremely difficult to establish as cell lines or xenografts. In this article, we describe a new series of prostate cancer xenografts propagated in athymic mice, designated LuCaP 23, developed from prostate metastases harvested at autopsy shortly after death. Tumor from three separate metastatic deposits was developed into three xenograft sublines: two from lymph node metastases (LuCaP 23.1 and 23.8) and one from a liver metastasis (LuCaP 23.12). Fluorescence in situ hybridization analysis confirms the xenografts are human. Histologically, the xenografts are comprised of columnar epithelial cells arranged in a glandular pattern. Tumor doubling times range from 11 to 21 days for the three sublines. The cells secrete large amounts of prostate-specific antigen (PSA) with PSA indices of 1.27, 1.63, and 5.21 ng/ml/mm3 for the mice bearing the LuCaP 23.1, 23.8, and 23.12 sublines, respectively. Following androgen deprivation a temporary decrease in PSA secretion and a decrease in tumor size are noted in most tumors. Eventually, the tumors become androgen independent and resume growth in castrate hosts. The degree of PSA response to castration and time to PSA nadir correlate with time to progression. Thus, unlike most existing models of prostatic carcinoma, this novel xenograft exhibits many phenotypic characteristics of clinical prostatic carcinoma, including androgen sensitivity. These properties make this xenograft an excellent model for future study.