Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.
Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.
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DOI：
10.1371/journal.pone.0046677
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tsao MS
中科院分区：
文献类型：
--
作者：
Leung L;Radulovich N;Zhu CQ;Organ S;Bandarchi B;Pintilie M;To C;Panchal D;Tsao MS
脂质运载蛋白2（LCN 2）是一种小的分泌蛋白，并且在胰腺癌以及其他癌症类型中观察到其表达升高。据报道，LCN 2促进对药物诱导的细胞凋亡的抗性，通过其与基质金属蛋白酶-9的物理缔合增强侵袭，并促进体内肿瘤生长。发现LCN 2通常在患者PDAC样本中表达，并且其免疫组化染色模式随着高级前体病变的严重程度增加而增强。在两个胰腺导管腺癌细胞系（BxPC 3和HPAF-II）与高LCN 2表达的LCN 2下调显着降低附着，侵袭和肿瘤生长在体内，但不增殖或运动。在两个胰腺导管腺癌细胞系（BxPC 3和HPAF-II）中下调LCN 2的高表达显著降低了体内的附着、侵袭和肿瘤生长。相反，在PANC 1中LCN 2过表达，内源性表达低，显著增加了侵袭，附着和增强肿瘤生长。抑制BxPC 3和HPAF-II细胞中的LCN 2增加了它们在体外对吉西他滨的敏感性，并且当测试BxPC 3时在体内增加了它们对吉西他滨的敏感性。此外，LCN 2促进VEGF和HIF 1A的表达，这有助于增强血管分布。这些总体结果表明，LCN 2在胰腺导管癌的恶性进展中起重要作用，并且是这种疾病的潜在治疗靶点。
Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.
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DOI：
10.1186/1756-9966-27-83
发表时间：
2008-12-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Shi H;Gu Y;Yang J;Xu L;Mi W;Yu W
通讯作者：
Yu W
胰腺癌的早期诊断：中性粒细胞明胶酶相关的脂肪蛋白作为胰腺上皮内肿瘤的标志。
影响因子：
8.8
作者：
Moniaux N;Chakraborty S;Yalniz M;Gonzalez J;Shostrom VK;Standop J;Lele SM;Ouellette M;Pour PM;Sasson AR;Brand RE;Hollingsworth MA;Jain M;Batra SK
通讯作者：
Batra SK
影响因子：
11.2
作者：
Leng, Xiaohong;Ding, Tian;Arlinghaus, Ralph B.
通讯作者：
Arlinghaus, Ralph B.
影响因子：
2.9
作者：
Goetz, DH;Willie, ST;Strong, RK
通讯作者：
Strong, RK
影响因子：
3.8
作者：
Mannelqvist, Monica;Stefansson, Ingunn M.;Akslen, Lars A.
通讯作者：
Akslen, Lars A.