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建立具有 FGFR2 过表达的新型硬癌胃癌细胞系 OCUM-14。

Establishment of a New Scirrhous Gastric Cancer Cell Line with FGFR2 Overexpression, OCUM-14.

机构信息

Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan.

Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka City, Japan.

出版信息

Ann Surg Oncol. 2019 Apr;26(4):1093-1102. doi: 10.1245/s10434-018-07145-2. Epub 2019 Jan 16.

Abstract

BACKGROUND

The prognosis of scirrhous gastric carcinoma (SGC), which is characterized by rapid infiltration and proliferation of cancer cells accompanied by extensive stromal fibrosis, is extremely poor. In this study, we report the establishment of a unique SGC cell line from a gastric cancer patient in whom an autopsy was performed.

METHODS

A new SGC cell line, OCUM-14, was established from malignant ascites of a male patient with SGC. A postmortem autopsy was performed on the patient. Characterization of OCUM-14 cells was analyzed by microscopic examination, reverse transcription polymerase chain reaction, fluorescence in situ hybridization analysis, immunohistochemical examination, CCK-8 assay, and in vivo assay.

RESULTS

OCUM-14 cells grew singly or in clusters, and were floating and round-shaped. Most OCUM-14 cells had many microvilli on their surfaces. The doubling time was 43.1 h, and the subcutaneous inoculation of 1.0 × 10 OCUM-14 cells into mice resulted in 50% tumor formation. mRNA expressions of fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) were observed in OCUM-14 cells. FGFR2, but not HER2, overexpression was found in OCUM-14 cells. The heterogeneous overexpression of FGFR2 was also found in both the primary tumor and metastatic lesions of the peritoneum, lymph node, bone marrow, and lung of the patient. The FGFR2 inhibitors AZD4547 and BGJ398 significantly decreased the growth of OCUM-14 cells, while paclitaxel and 5-fluorouracil significantly decreased the proliferation of OCUM-14 cells, but cisplatin did not.

CONCLUSION

A new gastric cancer cell line, OCUM-14, was established from SGC and showed FGFR2 overexpression. OCUM-14 might be useful for elucidating the characteristic mechanisms of SGC and clarifying the effect of FGFR2 inhibitors on SGC.

摘要

背景

以癌细胞快速浸润和增殖为特征并伴有广泛的基质纤维化的硬癌(SGC)预后极差。本研究报告了从一名进行尸检的 SGC 患者的恶性腹水中建立的独特 SGC 细胞系。

方法

从一名 SGC 男性患者的恶性腹水中建立了新的 SGC 细胞系 OCUM-14。对患者进行了尸检。通过显微镜检查、逆转录聚合酶链反应、荧光原位杂交分析、免疫组织化学检查、CCK-8 测定和体内测定分析 OCUM-14 细胞的特征。

结果

OCUM-14 细胞呈单个或簇状生长,呈悬浮和圆形。大多数 OCUM-14 细胞表面有许多微绒毛。倍增时间为 43.1 小时,将 1.0×10 OCUM-14 细胞皮下接种到小鼠中导致 50%的肿瘤形成。OCUM-14 细胞中观察到成纤维细胞生长因子受体 2(FGFR2)和人表皮生长因子受体 2(HER2)的 mRNA 表达。发现 OCUM-14 细胞中 FGFR2 过表达,但 HER2 不过表达。还发现患者的原发性肿瘤和腹膜、淋巴结、骨髓和肺部的转移病灶中 FGFR2 表达不均匀。FGFR2 抑制剂 AZD4547 和 BGJ398 显著降低 OCUM-14 细胞的生长,而紫杉醇和 5-氟尿嘧啶显著降低 OCUM-14 细胞的增殖,但顺铂没有。

结论

从 SGC 中建立了新的胃癌细胞系 OCUM-14,其显示 FGFR2 过表达。OCUM-14 可能有助于阐明 SGC 的特征机制,并阐明 FGFR2 抑制剂对 SGC 的作用。

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