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胰腺卫星细胞衍生的半乳糖凝集素-1促进胰腺导管腺癌的进展并降低其生存率。

Pancreatic satellite cells derived galectin-1 increase the progression and less survival of pancreatic ductal adenocarcinoma.

作者信息

Tang Dong, Zhang Jingqiu, Yuan Zhongxu, Gao Jun, Wang Sen, Ye Nianyuan, Li Ping, Gao Sujun, Miao Yi, Wang Daorong, Jiang Kuirong

机构信息

Department of General Surgery, Subei People's Hospital of Jiangsu Province (Clinic Medical College of Yang Zhou University), Yangzhou, Jiangsu Province, China.

Department of Digestive System, Subei People's Hospital of Jiangsu Province (Clinic Medical College of Yang Zhou University), Yangzhou, Jiangsu Province, China.

出版信息

PLoS One. 2014 Mar 4;9(3):e90476. doi: 10.1371/journal.pone.0090476. eCollection 2014.

Abstract

BACKGROUND

Galectin-1, a member of carbohydrate-binding proteins with a polyvalent function on tumor progression, was found strongly expressed in pancreatic satellite cells (PSCs), which partner in crime with cancer cells and promote the development of pancreatic ductal adenocarcinoma (PDAC). We evaluated the effects of PSCs derived Galectin-1 on the progression of PDAC, as well as the tumor establishment and development in mouse xenografts.

METHODS

The relationship between immunohistochemistry staining intensity of Galectin-1 and clinicopathologic variables were assessed in 66 PDAC tissues, 18 chronic pancreatitis tissues and 10 normal controls. The roles of PSCs isolated from PDAC and normal pancreas on the proliferative activity, MMP2 and MMP9 expression, and the invasion of CFPAC-1 in the co-cultured system, as well as on the tumor establishment and development in mouse xenografts by mixed implanting with CFPAC-1 subcutaneously were evaluated.

RESULTS

Galectin-1 expression was gradually increased from normal pancreas (negative), chronic pancreatitis (weak) to PDAC (strong), in which Galectin-1 expression was also increased from well, moderately to poorly differentiated PDAC. Galectin-1 staining intensity of pancreatic cancer tissue was associated with increase in tumor size, lymph node metastasis, perineural invasion and differentiation and UICC stage, and served as the independent prognostic indicator of poor survival of pancreatic cancer. In vitro and in vivo experiments indicated that TGF-β1 upregulated Galectin-1 expression in PSCs, which could further promotes the proliferative activity, MMP2 and MMP9 expression, and invasion of pancreatic cancer cells, as well as the tumor establishment and growth.

CONCLUSION

Galectin-1 expression in stromal cells of pancreatic cancer suggests that this protein plays a role in the promotion of cancer cells invasion and metastasis and provides a therapeutic target for the treatment of pancreatic cancer.

摘要

背景

半乳糖凝集素-1是一种对肿瘤进展具有多价功能的碳水化合物结合蛋白成员,在胰腺卫星细胞(PSC)中高表达,胰腺卫星细胞与癌细胞协同作用,促进胰腺导管腺癌(PDAC)的发展。我们评估了PSC来源的半乳糖凝集素-1对PDAC进展的影响,以及对小鼠异种移植瘤中肿瘤形成和发展的影响。

方法

在66例PDAC组织、18例慢性胰腺炎组织和10例正常对照中评估半乳糖凝集素-1免疫组化染色强度与临床病理变量之间的关系。评估从PDAC和正常胰腺分离的PSC在共培养系统中对CFPAC-1增殖活性、MMP2和MMP9表达以及侵袭的作用,以及通过与CFPAC-1皮下混合植入对小鼠异种移植瘤中肿瘤形成和发展的作用。

结果

半乳糖凝集素-1表达从正常胰腺(阴性)、慢性胰腺炎(弱阳性)到PDAC(强阳性)逐渐增加,其中从高分化、中分化到低分化PDAC,半乳糖凝集素-1表达也增加。胰腺癌组织的半乳糖凝集素-1染色强度与肿瘤大小增加、淋巴结转移、神经周围侵犯、分化程度和UICC分期相关,是胰腺癌患者不良生存的独立预后指标。体外和体内实验表明,TGF-β1上调PSC中半乳糖凝集素-1表达,进而可促进胰腺癌细胞的增殖活性、MMP2和MMP9表达以及侵袭,以及肿瘤形成和生长。

结论

胰腺癌基质细胞中的半乳糖凝集素-1表达表明该蛋白在促进癌细胞侵袭和转移中起作用,并为胰腺癌治疗提供了一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/859b/3942444/b9491c1a7a83/pone.0090476.g001.jpg

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