Generation and characterization of novel canine malignant mast cell line CL1.

Generation and characterization of novel canine malignant mast cell line CL1.
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DOI:
10.1016/j.vetimm.2008.09.027
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发表时间:
2009-01-15
影响因子:
1.8
通讯作者:
London CA
London CA
中科院分区:
农林科学3区
文献类型:
--
作者:
Lin TY;Thomas R;Tsai PC;Breen M;London CA

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使用目前可用的恶性犬肥大细胞系和骨髓来源的培养肥大细胞(BMCMC)进行的研究提供了对正常和肿瘤性犬肥大细胞生物学的深入了解。然而,许多目前可用的恶性犬肥大细胞系具有局限性,包括细胞表面标志物的丢失和无法结合犬IgE。我们最近从一只被诊断患有系统性肥大细胞增多症和肿瘤性渗出的 11 岁绝育雌性拉布拉多猎犬中产生了一种新型肥大细胞系 CL1。 CL1 细胞表达 KIT、FcεRI、CD44、CD45、CD14、CD11a、CD11b 和 CD18 以及糜酶。有趣的是,这些细胞表达野生型KIT,没有自磷酸化的证据,但能够在不添加外源干细胞因子(SCF)、KIT配体的情况下独立增殖。然而,用 SCF 刺激 CL1 细胞会诱导 KIT 磷酸化,从而促进细胞增殖。 CL1 细胞保留肥大细胞的功能特性,响应 IgE 交联和化学刺激,以剂量依赖性方式脱颗粒。最后,细胞遗传学评估揭示了 CL1 系中一些复发性肿瘤相关染色体拷贝数不平衡。总之,CL1细胞系具有与犬BMCMC相似的表型和功能特性,并且可能成为研究肥大细胞生物学、调节肥大细胞转化的因素、肥大细胞肿瘤的细胞遗传学异常和新型临床前疗法的有用工具。
Studies using the currently available malignant canine mast cell lines and bone marrow-derived cultured mast cells (BMCMCs) have provided an in-depth understanding of normal and neoplastic canine mast cell biology. However, many of the currently available malignant canine mast cell lines possess limitations, including loss of cell surface markers and inability to bind canine IgE. We have recently generated a novel mast cell line, CL1, from an 11-year-old spayed female Labrador retriever diagnosed with systemic mastocytosis and neoplastic effusion. The CL1 cells express KIT, FcεRI, CD44, CD45, CD14, CD11a, CD11b and CD18 as well as chymase. Interestingly, these cells express wild-type KIT, with no evidence of autophosphorylation, but are able to proliferate independently without the addition of exogenous stem cell factor (SCF), KIT ligand. However, stimulation of CL1 cells with SCF induces KIT phosphorylation promoting cell proliferation. The CL1 cells retain functional properties of mast cells, degranulating in a dose-dependent manner in response to both IgE cross-linking and chemical stimulation. Lastly, cytogenetic evaluation revealed several recurrent tumor-associated chromosome copy number imbalances in the CL1 line. In summary, the CL1 cell-line possesses phenotypic and functional properties similar to those found in canine BMCMCs, and will likely be a useful tool to study mast cell biology, factors regulating transformation of mast cells, cytogenetic abnormalities in mast cell tumors, and novel preclinical therapies.
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