Wang Yushen, Li Xianju, Wang Yi, Qin Jun
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, People's Republic of China.
Cancer Cell Int. 2025 Jan 12;25(1):9. doi: 10.1186/s12935-024-03633-6.
The aim of this study was to establish a primary mouse gastric carcinoma cell line.
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.
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.
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.
本研究的目的是建立一种原发性小鼠胃癌细胞系。
使用N-甲基-N-亚硝基脲和2%氯化钠溶液在具有免疫活性的BALB/c小鼠体内诱导胃体部腺癌。将新鲜的胃癌组织样本在补充有10%胎牛血清的1640培养基中进行原代培养和传代培养。通过光学显微镜评估细胞形态，并建立细胞生长曲线。进行基因组和蛋白质组分析以表征细胞系的分子特征。该细胞系在BALB/c小鼠中形成皮下肿瘤的成功率为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。在我们的临床前研究中，使用MEK抑制剂曲美替尼作为模型化合物。
从BALB/c小鼠中建立了一种新的胃癌细胞系，命名为MCC。该细胞系的倍增时间约为33小时。基因组和蛋白质组分析确定了临床胃癌患者中常见的突变，如Kras、Egfr和Ccnd3。此外，MCC过表达包括SLC1A5、MCM6和ITGA2在内的蛋白质，与相邻的非癌组织相比，这些蛋白质在胃癌组织中显著上调。MCC细胞系在具有免疫活性的BALB/c小鼠中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图谱非常相似。这种高度一致性有助于确定几种潜在的胃癌治疗靶点。曲美替尼的临床前研究表明，治疗可有效抑制胃癌生长，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细胞系是胃癌研究不可或缺的模型，为研究肿瘤发生和发展提供了一个强大的平台。其出色的致瘤能力以及与临床蛋白质组图谱的高度一致性凸显了其在转化研究中的重要性，有助于发现新的治疗靶点并阐明对制定有效治疗策略至关重要的分子途径。
