Establishment of cell line and in vivo mouse model of canine Langerhans cell histiocytosis
Establishment of cell line and in vivo mouse model of canine Langerhans cell histiocytosis
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犬朗格汉斯细胞组织细胞增多症细胞系及体内小鼠模型的建立
DOI：
10.1111/vco.12476
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发表时间：
2019
影响因子：
2.1
通讯作者：
Nakayama Hiroyuki
中科院分区：
文献类型：
--
作者：
Son Nguyen V.;Uchida Kazuyuki;Thongtharb Atigan;Chambers James K.;Kishimoto Takuya E.;Tomiyasu Hirotaka;Ohmi Aki;Tsujimoto Hajime;Nakayama Hiroyuki
从诊断为朗格汉斯细胞组织细胞增多症（LCH）的狗身上提取了一株名为FB‐LCH01的细胞系，并对其进行了鉴定。FB‐LCH01具有C形核仁，其特征是染色体模态畸变。原始肿瘤细胞和建立的FB - LCH01细胞对人白细胞抗原- DR、Iba - 1和E - cadherin免疫阳性，对CD163和CD204免疫阴性，提示Langerhans细胞来源。此外，我们还将FB‐LCH01的特征与先前建立的两种犬组织细胞肉瘤细胞系（PWC‐HS01和FCR‐HS02）的特征进行了比较。E‐cadherin仅在FB‐LCH01中表达，而在PWC‐HS01和FCR‐HS02中未表达。所有（n = 9）接种FB - LCH01细胞的严重联合免疫缺陷小鼠在3周后出现皮下肿瘤肿块。9只小鼠中有8只在淋巴结（8/8;100%）、肺（5/8;62.5%）、胃（5/8;62.5%）、心脏（4/8;50%）、胰腺（4/8;50%）、肾脏（3/8;37.5%）、皮肤（3/8;37.5%）和骨髓（1/8;12.5%）发生转移性病变。肿瘤细胞呈多形性，呈圆形或多角形，有明显的细胞异位和异核症。异种移植肿瘤细胞保持了原肿瘤的免疫组织化学特征，在注射部位和一些内脏器官持续表达E‐cadherin。总之，本研究建立的细胞系和小鼠异种移植模型反映了犬LCH的性质，可能为研究该病的病理肿瘤发生和治疗提供有希望的模型。
A cell line named FB‐LCH01, derived from a dog diagnosed with Langerhans cell histiocytosis (LCH), was established and characterized. FB‐LCH01 had C‐shaped nucleoli, characterized by modal chromosome aberrations. The original tumour cells as well as established FB‐LCH01 cells were immunopositive for human leukocyte antigen‐DR, Iba‐1 and E‐cadherin, and immunonegative for CD163 and CD204, suggesting Langerhans cell origin. Furthermore, the characteristics of FB‐LCH01 were compared with those of two canine histiocytic sarcoma cell lines (PWC‐HS01 and FCR‐HS02) established previously. Expression of E‐cadherin was detected only in FB‐LCH01, but not in PWC‐HS01 and FCR‐HS02. All (n = 9) the severe combined immunodeficiency mice inoculated with the FB‐LCH01 cells developed subcutaneous tumour masses after 3 weeks. Eight of nine mice also developed metastatic lesions in the lymph nodes (8/8; 100%), lung (5/8; 62.5%), stomach (5/8; 62.5%), heart (4/8; 50%), pancreas (4/8; 50%), kidney (3/8; 37.5%), skin (3/8; 37.5%) and bone marrow (1/8; 12.5%). Tumour cells were pleomorphic and round‐ to polygonal‐shaped with prominent anisocytosis and anisokaryosis. The xenotransplanted tumour cells maintained the immunohistochemical features of the original tumour with persistent E‐cadherin expression at injection site and some visceral organs. In conclusion, the established cell line as well as the mice xenotransplant model in this study reflect the nature of canine LCH and may serve as promising models for investigating the patho‐tumorigenesis and therapy of the disease.