Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells.
Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells.
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DOI：
10.18632/oncotarget.3572
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Novelli F
中科院分区：
文献类型：
--
作者：
Principe M;Ceruti P;Shih NY;Chattaragada MS;Rolla S;Conti L;Bestagno M;Zentilin L;Yang SH;Migliorini P;Cappello P;Burrone O;Novelli F
胰腺导管腺癌（PDAC）是一种高度侵袭性的恶性肿瘤，其特点是进展迅速、具有侵袭性和治疗耐药性。我们之前已经证明，大多数 PDAC 患者都有针对糖酵解酶 α-烯醇化酶 (ENO1) 的循环抗体，这与更好的治疗反应和生存相关。 ENO1 是一种代谢酶，也在细胞表面表达，充当纤溶酶原受体。 ENO1 通过促进纤溶酶原激活为纤溶酶（一种参与细胞外基质降解的丝氨酸蛋白酶），在细胞侵袭和转移中发挥至关重要的作用。本研究的目的是探讨ENO1在PDAC细胞侵袭中的作用。我们观察到 ENO1 在大多数 PDAC 细胞系的细胞表面表达。小鼠抗人ENO1单克隆抗体可抑制纤溶酶原依赖性人PDAC细胞的侵袭，并且其在免疫抑制小鼠中的转移扩散受到抑制。值得注意的是，在注射 PDAC 细胞的免疫抑制小鼠中，单次施用表达编码 72/1 抗 ENO1 mAb 的腺相关病毒 (AAV) cDNA 可以减少肺转移的数量。总体而言，这些数据表明 ENO1 参与 PDAC 细胞侵袭，并且抗 ENO1 mAb 的施用可以作为一种新的治疗选择来提高转移性 PDAC 患者的生存率。
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by rapid progression, invasiveness and resistance to treatment. We have previously demonstrated that most PDAC patients have circulating antibodies against the glycolytic enzyme alpha-enolase (ENO1), which correlates with a better response to therapy and survival. ENO1 is a metabolic enzyme, also expressed on the cell surface where it acts as a plasminogen receptor. ENO1 play a crucial role in cell invasion and metastasis by promoting plasminogen activation into plasmin, a serine-protease involved in extracellular matrix degradation. The aim of this study was to investigate the role of ENO1 in PDAC cell invasion. We observed that ENO1 was expressed on the cell surface of most PDAC cell lines. Mouse anti-human ENO1 monoclonal antibodies inhibited plasminogen-dependent invasion of human PDAC cells, and their metastatic spreading in immunosuppressed mice was inhibited. Notably, a single administration of Adeno-Associated Virus (AAV)-expressing cDNA coding for 72/1 anti-ENO1 mAb reduced the number of lung metastases in immunosuppressed mice injected with PDAC cells. Overall, these data indicate that ENO1 is involved in PDAC cell invasion, and that administration of an anti-ENO1 mAb can be exploited as a novel therapeutic option to increase the survival of metastatic PDAC patients.
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与腺相关的病毒基因疗法的进步：探索新的视野。
DOI：
10.3410/m3-17
发表时间：
2011
期刊：
F1000 medicine reports
影响因子：
--
作者：
Aalbers CJ;Tak PP;Vervoordeldonk MJ
通讯作者：
Vervoordeldonk MJ
影响因子：
37.3
作者：
Keleg, Shereen;Buchler, Peter;Ludwig, Roman;Buchler, Markus W;Friess, Helmut
通讯作者：
Friess, Helmut
影响因子：
4.1
作者：
LUND, LR;ELLIS, V;DANO, K
通讯作者：
DANO, K
影响因子：
6.4
作者：
LIEBER, M;MAZZETTA, J;TODARO, G
通讯作者：
TODARO, G
影响因子：
29.4
作者：
Cappello, Paola;Rolla, Simona;Novelli, Francesco
通讯作者：
Novelli, Francesco