Characterization of a Novel Murine Colon Carcinoma Subline with High-Metastatic Activity Established by In Vivo Selection Method
Characterization of a Novel Murine Colon Carcinoma Subline with High-Metastatic Activity Established by In Vivo Selection Method
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DOI：
10.3390/ijms21082829
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Shimokawa, Takashi
中科院分区：
文献类型：
--
作者：
Ma, Liqiu;Sakamoto, Yoshimitsu;Shimokawa, Takashi
建立具有不同转移能力的肿瘤细胞系被认为是研究肿瘤转移机制的有效途径。采用连续皮下移植的方法，从亲代结肠癌细胞系Colon-26中筛选出高转移潜能的小鼠结肠癌细胞亚系Colon-26 MGS。为了阐明参与转移增强的机制，比较了Colon-26 MGS和亲本细胞之间的形态学特征、细胞增殖和基因表达谱。Colon-26 MGS的转移能力是亲本细胞的10倍以上，但形态学特征和体外增殖率无差异。此外，结肠癌26 MGS荷瘤小鼠的脾细胞数量和肺转移前生态位与无瘤小鼠相比没有明显变化，但与结肠癌26荷瘤小鼠相比有显著差异。RNA-seq分析表明免疫共刺激分子在Colon-26 MGS中显著上调。这些结果表明，与亲本Colon-26相比，Colon-26 MGS不仅显示出更高的转移活性，而且显示出更低的宿主免疫应答诱导特性。Colon-26 MGS已被证明是研究涉及转移增强的多种机制的新的有用工具。
The establishment of cancer cell lines, which have different metastatic abilities compared with the parental cell, is considered as an effective approach to investigate mechanisms of metastasis. A highly metastatic potential mouse colon cancer cell subline, Colon-26MGS, was derived from the parental cell line Colon-26 by in vivo selection using continuous subcutaneous implanting to immunocompetent mice. To clarify the mechanisms involved in the enhancement of metastasis, morphological characteristics, cell proliferation, and gene expression profiles were compared between Colon-26MGS and the parental cell. Colon-26MGS showed over 10 times higher metastatic ability compared with the parental cell, but there were no differences in morphological characteristics and in vitro proliferation rates. In addition, the Colon-26MGS-bearing mice exhibited no marked change of splenocyte population and lung pre-metastatic niche with tumor-free mice, but there were significant differences compared to Colon-26-bearing mice. RNA-seq analyses indicated that immune costimulatory molecules were significantly up-regulated in Colon-26MGS. These results suggest that Colon-26MGS showed not only higher metastatic activity, but also less induction property of host immune response compared to parental Colon-26. Colon-26MGS has proven to be a novel useful tool for studying multiple mechanisms involving metastasis enhancement.