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犬甲状腺癌:分子特征及裸鼠中的细胞系生长。

Canine Thyroid Cancer: Molecular Characterization and Cell Line Growth in Nude Mice.

机构信息

Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

出版信息

Vet Pathol. 2020 Mar;57(2):227-240. doi: 10.1177/0300985819901120. Epub 2020 Feb 21.

DOI:10.1177/0300985819901120
PMID:32081094
Abstract

Thyroid cancer is the most common endocrine malignancy in dogs. Dogs and humans are similar in the spontaneous development of thyroid cancer and metastasis to lungs; however, thyroid cancer has a higher incidence of metastasis in dogs. This study developed a preclinical nude mouse model of canine thyroid cancer using a canine thyroid adenocarcinoma cell line (CTAC) and measured the expression of important invasion and metastasis genes in spontaneous canine thyroid carcinomas and CTAC cells. CTAC cells were examined by electron microscopy. Short tandem repeat analysis was performed for both the original neoplasm and CTAC cells. CTAC cells were transduced with luciferase and injected subcutaneously and into the tail vein. Tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Invasion and metastasis genes were characterized in 8 follicular thyroid carcinomas (FTCs), 4 C-cell thyroid carcinomas, 3 normal thyroids, and CTAC cells. CTAC cells grew well as xenografts in the subcutis, and they resembled the primary neoplasm. Metastasis to the kidney and lung occurred infrequently following subcutaneous and tail vein injection of CTAC cells. STR analysis confirmed that CTAC cells were derived from the original neoplasm and were of canine origin. Finally, 24 genes were differentially expressed in spontaneous canine thyroid carcinomas, CTAC, and normal thyroids. This study demonstrated the usefulness of a nude mouse model of experimental canine thyroid carcinoma and identified potential molecular targets of canine follicular and C-cell thyroid carcinoma.

摘要

甲状腺癌是犬类最常见的内分泌恶性肿瘤。犬类和人类在甲状腺癌的自发发展和肺部转移方面具有相似性;然而,甲状腺癌在犬类中转移的发生率更高。本研究使用犬甲状腺腺癌细胞系(CTAC)建立了犬甲状腺癌的临床前裸鼠模型,并测量了自发性犬甲状腺癌和 CTAC 细胞中重要侵袭和转移基因的表达。通过电子显微镜检查 CTAC 细胞。对原始肿瘤和 CTAC 细胞均进行短串联重复分析。将荧光素酶转导到 CTAC 细胞中,并皮下注射和尾静脉注射。使用生物发光成像监测肿瘤和转移,并通过大体尸检和组织病理学进行确认。在 8 例滤泡状甲状腺癌(FTC)、4 例 C 细胞甲状腺癌、3 例正常甲状腺和 CTAC 细胞中对侵袭和转移基因进行了特征描述。CTAC 细胞在皮下作为异种移植物生长良好,并且与原发性肿瘤相似。皮下和尾静脉注射 CTAC 细胞后,肾脏和肺部转移很少发生。STR 分析证实 CTAC 细胞来源于原始肿瘤,且具有犬类来源。最后,在自发性犬甲状腺癌、CTAC 和正常甲状腺中,有 24 个基因表达存在差异。本研究证明了实验性犬甲状腺癌裸鼠模型的有用性,并确定了犬甲状腺滤泡和 C 细胞癌的潜在分子靶标。

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