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Abstract：
Trefoil factor family member 2 (Tff2) is significantly involved in intestinal tumor growth in ApcMin/+ mice, which can be used as a human colon cancer model. TFF2, which encodes TFF2 (spasmolytic protein 1) is highly expressed in human cancer tissues, including the pancreas, colon and bile ducts, as well as in normal gastric and duodenum tissues. By contrast, TFF2 exhibits low expression levels in other normal tissues, including the small and large intestine. Furthermore, TFF2 expression has not been detected in DLD-1 cells, a cell line derived from human colon cancer. What induces TFF2 expression in normal and tumor cells is still unknown. Highly malignant tumor tissues are characterized by higher temperatures and lower pH (6.2-6.9) than in normal tissues, where normal pH ranges from 7.2 to 7.4. This microenvironment exacerbates malignancy by promoting the acquisition of cell death resistance, drug resistance and immune escape. Therefore, the present study examined how TFF2 expression is affected in cultured cells that imitate the tumor tissue microenvironment. The incubation temperature was increased from 37 to 40°C, but no expression of TFF2 was induced. Subsequently, a culture solution with an acidic pH was prepared to simulate the Warburg effect in tumors. TFF2 expression was increased by 42.8- and 5.8-fold in cells cultured in acidic medium at pH 6.5 and 6.8 compared with at pH 7.4, respectively, as determined using the relative quantification method following quantitative polymerase chain reaction. The present study also analyzed fluctuations in the expression levels of genes other than TFF2, under acidic conditions. Acidic conditions upregulated the expression of genes related to cell membranes and glycoproteins, based on the Database for Annotation, Visualization, and Integrated Discovery. In conclusion, TFF2 was highly expressed under acidic conditions, implying that it may have an important function in protecting the plasma membrane from acidic environments in both normal and cancer cells. These findings warrant further investigation of TFF2 as a target of cancer therapy and diagnosis.
摘要：
三叶因子家族成员2(Tff2)显著参与ApcMin/+小鼠肠道肿瘤的生长,可用作人类结肠癌模型。TFF2编码TFF2(解痉挛蛋白1)在人类癌组织中高表达,包括胰腺,结肠和胆管，以及正常的胃和十二指肠组织。相比之下,TFF2在其他正常组织中表现出低表达水平，包括小肠和大肠。此外，在DLD-1细胞中未检测到TFF2表达，来源于人类结肠癌的细胞系。在正常细胞和肿瘤细胞中诱导TFF2表达的原因仍然未知。高度恶性肿瘤组织的特征是比正常组织更高的温度和更低的pH（6.2-6.9），其中正常pH范围为7.2至7.4。这种微环境通过促进细胞死亡抗性的获得而加剧恶性肿瘤，耐药性和免疫逃逸。因此,本研究检查了TFF2表达如何在模拟肿瘤组织微环境的培养细胞中受到影响。孵育温度从37°C增加到40°C,但未诱导TFF2的表达。随后，制备具有酸性pH的培养液以模拟肿瘤中的Warburg效应。与pH7.4相比，在pH6.5和6.8的酸性培养基中培养的细胞中TFF2表达分别增加了42.8和5.8倍，如使用定量聚合酶链反应后的相对定量方法所确定的。本研究还分析了在酸性条件下除TFF2以外的基因的表达水平的波动。酸性条件上调细胞膜和糖蛋白相关基因的表达，基于注释数据库，可视化,和集成发现。总之,TFF2在酸性条件下高表达,这意味着它可能在保护质膜免受正常细胞和癌细胞酸性环境的影响方面具有重要功能。这些发现保证了对TFF2作为癌症治疗和诊断靶标的进一步研究。
