Establishment and characterization of a new mouse gastric carcinoma cell line, MCC.

IF 5.3 2区 医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2025-01-12 DOI:10.1186/s12935-024-03633-6
Yushen Wang, Xianju Li, Yi Wang, Jun Qin
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Abstract

Background: The aim of this study was to establish a primary mouse gastric carcinoma cell line.

Methods: Gastric adenocarcinoma in the body region was induced in immunocompetent BALB/c mice using N-Methyl-N-nitrosourea and a 2% NaCl solution. Fresh gastric cancer tissue samples were cultured in 1640 medium supplemented with 10% fetal bovine serum for primary culture and subculture. Cellular morphology was assessed via light microscopy, and a cell growth curve was established. Genomic and proteomic analyses were conducted to characterize the molecular features of the cell lines. This cell line demonstrated a 100% success rate in forming subcutaneous tumors in BALB/c mice. By integrating proteomic profiles from clinical gastric cancer patients and the murine subcutaneous tumor model, several molecular targets suitable for preclinical investigation were identified. Trametinib, a MEK inhibitor, was employed as a model compound in our preclinical study.

Results: A novel gastric carcinoma cell line, designated MCC, was established from BALB/c mice. This cell line exhibited a doubling time of approximately 33 h. Genomic and proteomic analyses identified mutations frequently observed in clinical gastric cancer patients, such as Kras, Egfr, and Ccnd3. Additionally, MCC overexpresses proteins, including SLC1A5, MCM6, and ITGA2, which are significantly upregulated in gastric cancer tissues compared to adjacent non-cancerous tissues. The MCC cell line demonstrated stable tumorigenicity in immunocompetent BALB/c mice, forming subcutaneous tumors that closely resemble the proteomic profile of clinical gastric cancer samples. This high concordance facilitated the identification of several potential therapeutic targets for gastric cancer. Preclinical studies with trametinib revealed that treatment effectively inhibited gastric cancer growth, likely mediated through the activation of immune cells, particularly neutrophils and T cells.

Conclusions: The MCC cell line serves as an indispensable model for gastric cancer research, offering a robust platform for investigating tumor development and progression. Its exceptional tumorigenic capacity and strong concordance with clinical proteomic profiles underscore its significance in translational research, facilitating the discovery of novel therapeutic targets and elucidation of molecular pathways critical for developing effective treatment strategies.

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小鼠胃癌新细胞系MCC的建立与鉴定。
背景:本研究旨在建立小鼠原代胃癌细胞系:本研究旨在建立小鼠原代胃癌细胞系:方法:使用 N-甲基-N-亚硝基脲和 2% 氯化钠溶液诱导免疫功能正常的 BALB/c 小鼠体部胃腺癌。新鲜胃癌组织样本在添加 10% 胎牛血清的 1640 培养基中进行原代培养和亚培养。通过光学显微镜评估细胞形态,并建立细胞生长曲线。为确定细胞系的分子特征,还进行了基因组和蛋白质组分析。该细胞系在 BALB/c 小鼠皮下形成肿瘤的成功率为 100%。通过整合临床胃癌患者和小鼠皮下肿瘤模型的蛋白质组图谱,确定了几个适合临床前研究的分子靶点。我们在临床前研究中使用了 MEK 抑制剂曲美替尼作为模型化合物:结果:从 BALB/c 小鼠体内建立了一种新型胃癌细胞系,命名为 MCC。该细胞系的倍增时间约为 33 h。基因组和蛋白质组分析发现了临床胃癌患者常出现的突变,如 Kras、Egfr 和 Ccnd3。此外,MCC 还过度表达 SLC1A5、MCM6 和 ITGA2 等蛋白,与邻近的非癌组织相比,这些蛋白在胃癌组织中明显上调。MCC 细胞系在免疫功能正常的 BALB/c 小鼠体内表现出稳定的致瘤性,形成的皮下肿瘤与临床胃癌样本的蛋白质组特征非常相似。这种高度一致性有助于确定胃癌的几个潜在治疗靶点。曲美替尼的临床前研究显示,治疗可有效抑制胃癌生长,这可能是通过激活免疫细胞,特别是中性粒细胞和T细胞介导的:MCC 细胞系是胃癌研究中不可或缺的模型,为研究肿瘤的发展和进展提供了一个强大的平台。其卓越的致瘤能力和与临床蛋白质组图谱的高度一致性突出了其在转化研究中的重要意义,有助于发现新的治疗靶点和阐明对制定有效治疗策略至关重要的分子通路。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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