Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell poorly differentiated adenocarcinoma cell lines with low and high malignant potential
Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell poorly differentiated adenocarcinoma cell lines with low and high malignant potential
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DOI：
10.1007/s10120-012-0149-2
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发表时间：
2013-01-01
期刊：
影响因子：
7.4
通讯作者：
Kodera, Yasuhiro
中科院分区：
文献类型：
--
作者：
Murakami, Hiroki;Nakanishi, Hayao;Kodera, Yasuhiro
背景低分化印戒细胞癌（SRCC）和非印戒细胞癌（NSRCC）是胃癌中常见的两种组织学亚型，具有不同的形态学特征。然而，由于现有细胞系的限制，迄今为止，其生长、分化和转移的分子基础仍不清楚。我们建立了新的SRCC和NSRCC细胞系，GPM-2和GPM-1分别来自两名胃癌腹膜转移患者的腹水。qRT-PCR）分析显示GPM-2细胞显示胃和肠分化表型（E-cadherin+/MUC 5AC +/MUC 6 +/Villin+），并在裸鼠中形成具有典型SRCC组织学的异种移植瘤。相比之下，GPM-1细胞仅弱表达分化标记物，显示出E-cadherin（低）+/MUC 2-/MUC 5AC-/Villin（低）+的表型。特征性地，发现GPM-2细胞高度表达膜结合粘蛋白（MUC 1/MUC 4）和分泌粘蛋白糖蛋白（MUC 5AC/MUC 6），其表达受表观遗传机制如组蛋白乙酰化调节。GPM-2细胞也分泌大量sTn抗原到培养基中。GPM-2细胞的这些粘蛋白谱与常规SRCC细胞系（KATO III和HSC-39）的粘蛋白谱不同，常规SRCC细胞系优先表达肠MUC 2/MUC 4以及sLe（x）和sLe（A）抗原。结论新的SRCC细胞系GPM-2细胞比NSRC型GPM-1细胞分化程度更高，侵袭性更低，为进一步研究SRCC细胞生长、分化、转移的分子机制提供了良好的模型。以及SRCC胃癌细胞系的粘蛋白产生。
Background Poorly differentiated signet-ring cell carcinoma (SRCC) and non signet-ring cell carcinoma (NSRCC) are prevalent histological subtypes of gastric cancers with distinct morphological features. To date, however, the molecular basis of their growth, differentiation, and metastasis still remains unclear, because of the limitation of available cell lines.Methods In the present study, we established novel SRCC and NSRCC cell lines (designated GPM-2 and GPM-1) derived from the ascites of two individual gastric cancer patients with peritoneal metastasis.Results Immunohistochemical and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that GPM-2 cells showed both gastric and intestinal differentiation phenotypes (E-cadherin+/MUC5AC+/MUC6+/Villin+), and formed xenografted tumors with typical SRCC histology in nude mice. In contrast, GPM-1 cells only weakly expressed differentiation markers, showing a phenotype of E-cadherin(low) +/MUC2-/MUC5AC-/Villin (low) +. Characteristically, GPM-2 cells were found to highly express both membrane-bound mucin (MUC1/MUC4) and secreted mucin glycoproteins (MUC5AC/MUC6), whose expression is regulated by an epigenetic mechanism such as histone acetylation. GPM-2 cells also secreted a large amount of sTn antigen into the culture medium. These mucin profiles of GPM-2 cells are distinct from those of conventional SRCC cell lines (KATO III and HSC-39), which preferentially express intestinal MUC2/MUC4 as well as sLe(x) and sLe(A) antigens. In addition, GPM-2 cells showed a slow growth rate, and a lower metastatic potential than GPM-1 cells.Conclusions These results indicate that the cells of the new SRCC line, GPM-2 cells, are more differentiated and less aggressive than NSRCC-type GPM-1 cells, and would thus offer an excellent model for understanding the molecular mechanism underlying the growth, differentiation, and mucin production of an SRCC gastric cancer cell line.