Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs
Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs
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DOI：
10.3389/fonc.2019.00009
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发表时间：
2019-01-22
影响因子：
4.7
通讯作者：
Shapiro, Erik M.
中科院分区：
文献类型：
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作者：
Boettcher, Adeline N.;Kiupel, Matti;Shapiro, Erik M.
卵巢癌（OvCa）是最致命的妇科恶性肿瘤，三分之二的患者在诊断时患有晚期疾病（II-IV）。我们需要改进诊断和治疗方法，但卵巢癌研究的临床前动物模型主要局限于啮齿动物，因为这些动物的数据无法转化为临床。因此，目前需要一个大型动物OvCa模型。因此，我们试图确定在解剖学和生理学方面与人类更相似的猪是否会成为OvCa的可行临床前动物模型。我们将人类OSPC-ARK1细胞（一种耐化疗的原发性卵巢浆液乳头状癌细胞系）注射到饲养在新型生物防护设施中的四只严重联合免疫缺陷（SCID）猪和两只非SCID猪的颈部肌肉和耳组织中，以研究人类OvCa细胞在异种移植模型中形成肿瘤的能力。3头SCID猪的耳部组织出现肿瘤，2头SCID猪的颈部组织出现肿瘤；非scid对照猪未发现肿瘤。所有肿瘤在显微镜下均证实为卵巢癌。基于Claudin 3、Claudin 4、Cytokeratin 7、p16和EMA的表达，SCID猪的癌在形态学上与原始卵巢癌相似，具有相同的免疫组织化学表型。证实OSPC-ARK1细胞在SCID猪中形成癌，证实了猪OvCa原位模型的进一步发展。
Ovarian cancer (OvCa) is the most lethal gynecologic malignancy, with two-thirds of patients having late-stage disease (II-IV) at diagnosis. Improved diagnosis and therapies are needed, yet preclinical animal models for ovarian cancer research have primarily been restricted to rodents, for data on which can fail to translate to the clinic. Thus, there is currently a need for a large animal OvCa model. Therefore, we sought to determine if pigs, being more similar to humans in terms of anatomy and physiology, would be a viable preclinical animal model for OvCa. We injected human OSPC-ARK1 cells, a chemotherapy-resistant primary ovarian serous papillary carcinoma cell line, into the neck muscle and ear tissue of four severe combined immune deficient (SCID) and two non-SCID pigs housed in novel biocontainment facilities to study the ability of human OvCa cells to form tumors in a xenotransplantation model. Tumors developed in ear tissue of three SCID pigs, while two SCID pigs developed tumors in neck tissue; no tumors were detected in non-SCID control pigs. All tumor masses were confirmed microscopically as ovarian carcinomas. The carcinomas in SCID pigs were morphologically similar to the original ovarian carcinoma and had the same immunohistochemical phenotype based on expression of Claudin 3, Claudin 4, Cytokeratin 7, p16, and EMA. Confirmation that OSPC-ARK1 cells form carcinomas in SCID pigs substantiates further development of orthotopic models of OvCa in pigs.