Hassan B B, Elshafae S M, Supsavhad W, Simmons J K, Dirksen W P, Sokkar S M, Rosol T J
1 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
2 Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Vet Pathol. 2017 Jan;54(1):32-43. doi: 10.1177/0300985816650243. Epub 2016 Jul 11.
Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis.
猫乳腺肿瘤(FMC)在发病年龄、发病率、组织病理学特征、生物学行为和转移模式方面与人类乳腺癌相似。因此,FMC被认为是侵袭性人类乳腺癌的相关模型。本研究的目的是建立FMC肿瘤生长和转移的裸鼠模型,并检测FMC组织和细胞系中负责淋巴管生成、血管生成、肿瘤进展和淋巴结转移的基因表达。将两个原发性FMC组织皮下注射,将6个FMC细胞系注射到裸鼠的3个部位(皮下、胫骨内和心内)。使用生物发光成像监测肿瘤和转移情况,并通过大体尸检、放射学和组织病理学进行特征描述。在6个原发性FMC组织、2个皮下FMC异种移植瘤和6个FMC细胞系中,使用定量实时逆转录聚合酶链反应对FMC中侵袭和转移基因进行分子特征分析。皮下异种移植瘤的组织学表现与原发性肿瘤相似。皮下注射肿瘤组织和细胞系后未发现转移,而胫骨内和心内注射FMC细胞系后证实有肺、脑、肝、肾、眼和骨转移。最后,15个基因在FMC组织和细胞系中差异表达。所有样本中高表达的基因是PDGFA、PDGFB、PDGFC、FGF2、EGFR、ERBB2、ERBB3、VEGFD、VEGFR3和MYOF。三个基因(PDGFD、ANGPT2和VEGFC)被证实来源于基质。本研究证明了实验性FMC裸鼠模型的实用性,并确定了FMC进展和转移的分子靶点。