Li Jun, Xue Hongzhang, Xiang Zhen, Song Shuzheng, Yan Ranlin, Ji Jun, Zhu Zhenggang, Wei Chaochun, Yu Yingyan
Department of Surgery of Ruijin Hospital, Shanghai Institute of Digestive Surgery, and Shanghai Key Laboratory for Gastric Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Front Pharmacol. 2020 Jul 31;11:1183. doi: 10.3389/fphar.2020.01183. eCollection 2020.
A high serine content in body fluid was identified in a portion of patients with gastric cancer, but its biological significance was not clear. Here, we investigated the biological effect of serine on gastric cancer cells. Serine was added into the culture medium of MGC803 and HGC27 cancer cells, and its influence on multiple biological functions, such as cell growth, migration and invasion, and drug resistance was analyzed. We examined the global transcriptomic profiles in these cultured cells with high serine content. Both MGC803 and HGC27 cell lines were originated from male patients, however, their basal gene expression patterns were very different. The finding of cell differentiation-associated genes, ALPI, KRT18, TM4SF1, KRT81, A2M, MT1E, MUC16, BASP1, TUSC3, and PRSS21 in MGC803 cells suggested that this cell line was more poorly differentiated, compared to HGC27 cell line. When the serine concentration was increased to 150mg/ml in medium, the response of these two gastric cancer cell lines was different, particularly on cell growth, cell migration, and invasion and 5-FU resistance. In animal experiment, administration of high concentration of serine promoted cancer cell metastasis to local lymph node. Taken together, we characterized the basal gene expressing profiles of MGC803 and HGC27. The HGC27 cells were more differentiated than MGC803 cells. MGC803 cells were more sensitive to the change of serine content. Our results suggested that the responsiveness of cancer cells to microenvironmental change is associated with their genetic background.
在部分胃癌患者的体液中发现丝氨酸含量较高,但其生物学意义尚不清楚。在此,我们研究了丝氨酸对胃癌细胞的生物学作用。将丝氨酸添加到MGC803和HGC27癌细胞的培养基中,并分析其对多种生物学功能的影响,如细胞生长、迁移、侵袭和耐药性。我们检测了这些丝氨酸含量高的培养细胞的整体转录组谱。MGC803和HGC27细胞系均来源于男性患者,然而,它们的基础基因表达模式却非常不同。在MGC803细胞中发现细胞分化相关基因ALPI、KRT18、TM4SF1、KRT81、A2M、MT1E、MUC16、BASP1、TUSC3和PRSS21,表明与HGC27细胞系相比,该细胞系分化程度更低。当培养基中丝氨酸浓度增加到150mg/ml时,这两种胃癌细胞系的反应不同,特别是在细胞生长、细胞迁移、侵袭和5-氟尿嘧啶耐药性方面。在动物实验中,给予高浓度丝氨酸可促进癌细胞向局部淋巴结转移。综上所述,我们对MGC803和HGC27的基础基因表达谱进行了表征。HGC27细胞比MGC803细胞分化程度更高。MGC803细胞对丝氨酸含量的变化更敏感。我们的结果表明,癌细胞对微环境变化的反应性与其遗传背景有关。