Galectin-1基因高表达促进胃癌细胞血管生成机制的研究

发布时间：2018-05-22 11:07

本文选题：胃癌 + 血管生成　；参考：《扬州大学》2015年硕士论文

【摘要】：背景与目的：Galectin-1是聚糖结合蛋白Galectin家族成员之一,与β-半乳糖苷具有高亲和力,与受体结合启动了多种信号转导途径,参与细胞的黏附、增殖、凋亡和炎症反应等多种生理病理过程。Galectin-1在多种肿瘤组织的间质细胞中高表达,能促进肿瘤生长、增殖、促进肿瘤免疫抑制和血管形成以及侵袭转移等。近年来,研究发现,Galectit-1在胃癌相关成纤维细胞(Cancer Associated Fibroblasts, CAFs)中高表达,而Galectin-1和CAFs都与肿瘤细胞的血管生成密切相关,因此本研究的目的就是揭示起源于CAFs的Galectin-1高表达促进胃癌细胞血管生成的内在机制。方法：收集2012年1月至2012年12月江苏省苏北人民医院施行的全胃切除术47例胃癌组织和相应的癌旁组织标本(距切缘2cm),根据分化程度将组织标本分为正常胃组织,高级别上皮内瘤变胃组织,高分化、中分化和低分化胃癌组织,然后用免疫组织化学染色法研究不同分化程度细胞中Galectin-1与血管内皮生长因子(Vascular Endothelial Growth Factor, VEGF)以及血小板-内皮细胞粘附分子(CD31)表达程度的关系。从胃癌组织中分离出CAFs,并用小分子干扰RNA敲除相应基因,以抑制Galectin-1的表达,或者用重组质粒的方法促进其高表达,然后将处理后的CAFs与人脐静脉内皮细胞(HUVEC)共培养,检测小管形成能力；将CAFs与胃癌细胞共培养,检测其VEGF和VEGF受体(VEGFR-2)的表达情况。Galectin-1在活体的肿瘤血管生成中的作用,则用鸡胚绒毛膜尿囊实验进行研究。结果：在不同分化程度的细胞中,分化程度越低,Galectin-1的表达越强烈,并且与Galectin-1与VEGF和CD31的表达呈正相关。而在共培养体系中,Galectin-1的高表达能促进HUVEC的增殖、迁移和小管形成,并且能增强胃癌细胞VEGF的表达和VEGFR-2的磷酸化。鸡胚绒毛膜尿囊实验也表明源于CAFs的Galectin-1高表达能刺激肿瘤生长,促进肿瘤的新血管生成。与之相反,CAFs的Galectin-1基因表达被抑制后,这些效应也相应的受到抑制。结论：起源于CAFs的Galectin-1高表达能一定程度上促进胃癌细胞的新血管生成,因此Galectin-1可以作为抗肿瘤血管生成疗法的一个潜在靶点。
[Abstract]:Background & AIM: Galectin-1 is a member of the Galectin family of glycan binding proteins. It has high affinity to 尾 -galactoside and initiates many signal transduction pathways to participate in cell adhesion and proliferation. High expression of Galectin-1 in stromal cells of various tumor tissues, which can promote tumor growth, proliferation, tumor immunosuppression, angiogenesis, invasion and metastasis. In recent years, it has been found that Galectit-1 is highly expressed in cancer Associated Fibroblasts, CAFs), and that both Galectin-1 and CAFs are closely related to angiogenesis. The aim of this study was to reveal the mechanism of high expression of Galectin-1 derived from CAFs in promoting angiogenesis in gastric cancer cells. Methods: from January 2012 to December 2012, 47 cases of gastric cancer tissues and corresponding adjacent tissues were collected from Jiangsu Subei people's Hospital, Jiangsu Province. The specimens were divided into normal gastric tissues according to their differentiation degree. High grade intraepithelial rumen tissue, highly differentiated, moderately differentiated and poorly differentiated gastric cancer tissue, Then immunohistochemical staining was used to study the relationship between the expression of Galectin-1 and vascular Endothelial Growth Factor, VEGF) and platelet-endothelial cell adhesion molecule CD31 in differentiated cells. CAFs were isolated from gastric cancer tissues, and the corresponding genes were knockout by small interfering RNA to inhibit the expression of Galectin-1, or to promote its overexpression by recombinant plasmid. Then the treated CAFs was co-cultured with human umbilical vein endothelial cells (HUVECs). The expression of VEGF and VEGF receptor VEGFR-2 and the role of Galectin-1 in tumor angiogenesis in vivo were studied by chorioallantoic test. Results: the lower the differentiation degree, the stronger the expression of Galectin-1, and positively correlated with the expression of Galectin-1, VEGF and CD31. The high expression of Galectin-1 could promote the proliferation, migration and tubule formation of HUVEC, and enhance the expression of VEGF and the phosphorylation of VEGFR-2 in gastric cancer cells. Chorioallantoic assay also showed that high expression of Galectin-1 derived from CAFs could stimulate tumor growth and promote tumor angiogenesis. On the contrary, the expression of Galectin-1 gene in CAFs was inhibited, and these effects were also inhibited. Conclusion: the high expression of Galectin-1 derived from CAFs can promote the angiogenesis of gastric cancer cells to some extent, so Galectin-1 may be a potential target of antiangiogenic therapy.
【学位授予单位】：扬州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2

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