The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer

被引：44

作者：

Rawnaq, Tamina ^{[1
]}

Dietrich, Luisa ^{[1
]}

Wolters-Eisfeld, Gerrit ^{[1
]}

Uzunoglu, Faik G. ^{[1
]}

Vashist, Yogesh K. ^{[1
]}

Bachmann, Kai ^{[1
]}

Simon, Ronald ^{[2
]}

Izbicki, Jakob R. ^{[1
]}

Bockhorn, Maximilian ^{[1
]}

Guengoer, Cenap ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Inst Pathol, D-20246 Hamburg, Germany

来源：

MOLECULAR CANCER RESEARCH | 2014年 / 12卷 / 05期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; CARCINOMA-CELLS; EXPRESSION; GENE; PLEIOTROPHIN; CHEMORESISTANCE; NEUROBLASTOMA; RESECTION; BINDING; MARKER;

D O I：

10.1158/1541-7786.MCR-13-0467

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis among solid tumors and despite increased knowledge of the molecular mechanisms contributing to progression and metastasis, minimal progress has been done in establishing new targeted therapies for this deadly disease. The expression of the multifunctional growth/differentiation factor midkine (MK) promotes a variety of cellular functions leading to increased angiogenesis, proliferation, migration, and survival. Moreover, MK is intensively discussed as a potential new-therapy target and as biomarker for cancer progression and chemotherapeutic resistance in multiple cancers. Therefore, the present study investigated the molecular role of MK in pancreatic cancer. It was found that MK is elevated in PDAC and differentially expressed in other histologic subtypes of pancreatic cancer, whereas normal pancreatic cells did not express MK, thus making it an attractive candidate for targeted therapies. As a secreted growth/differentiation factor, MK was investigated as a biomarker in clinical serum specimens using ELISA. In addition, knockdown studies of MK revealed a link to proliferation and migration status in vitro. Finally, upstream signaling pathways were analyzed, with TNF-alpha and EGF being the main inductors of MK expression in PDAC.

引用

页码：670 / 680

页数：11

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