Shaw Tanya J, Senterman Mary K, Dawson Kerri, Crane Colleen A, Vanderhyden Barbara C
Ottawa Regional Cancer Centre, Department of Cellular and Molecular Medicine, University of Ottawa, ON, Canada K1H 1C4.
Mol Ther. 2004 Dec;10(6):1032-42. doi: 10.1016/j.ymthe.2004.08.013.
Improvement of ovarian cancer patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. Xenograft models are frequently used, but with little discussion of disease histology. The objectives of this study were to inject 11 ovarian cancer cell lines intraperitoneally (ip), and a subset intrabursally (ib; orthotopic), into nude mice and to analyze the resulting pathologies. Eight of 11 lines injected ip formed tumors within 3 months at variable rates with the following histological subtype distribution: one endometrioid, one serous, one clear cell, and five undifferentiated. Only mice injected with A2780-cp cells presented with ovarian-specific metastases (11 of 88), and the survival time of these animals was significantly shorter, which may be attributed to the higher proliferation rate as determined by Ki67 positivity. Additional analysis of the influence of the ovarian microenvironment on cell characteristics was conducted with ib injection of two cell lines (OVCA 429 and ES-2). The site of injection did not affect the tumor histology, the effect on proliferation was cell-type dependent, and the tumor take rate (cell survival) was negatively affected for OVCA 429 cells. The animal models described herein represent histologically distinct models of both early and late stage ovarian cancer useful for evaluation of therapeutics.
改善卵巢癌患者的治疗效果需要具备良好特征的动物模型来评估新型疗法。异种移植模型经常被使用，但对疾病组织学的讨论较少。本研究的目的是将11种卵巢癌细胞系经腹腔注射（ip），并将其中一部分经囊内注射（ib；原位）到裸鼠体内，然后分析由此产生的病理学情况。经腹腔注射的11种细胞系中有8种在3个月内以不同的速率形成了肿瘤，其组织学亚型分布如下：1种子宫内膜样癌、1种浆液性癌、1种透明细胞癌和5种未分化癌。只有注射了A2780 - cp细胞的小鼠出现了卵巢特异性转移（88只中有11只），这些动物的存活时间明显较短，这可能归因于通过Ki67阳性确定的较高增殖率。通过对两种细胞系（OVCA 429和ES - 2）进行囊内注射，进一步分析了卵巢微环境对细胞特征的影响。注射部位不影响肿瘤组织学，对增殖的影响因细胞类型而异，并且OVCA 429细胞的肿瘤形成率（细胞存活率）受到负面影响。本文所述的动物模型代表了组织学上不同的早期和晚期卵巢癌模型，可用于评估治疗方法。
