The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer
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The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer. / Rawnaq, Tamina; Dietrich, Luisa; Wolters-Eisfeld, Gerrit; Uzunoglu, Faik G; Vashist, Yogesh K; Bachmann, Kai; Simon, Ronald; Izbicki, Jakob R; Bockhorn, Maximilian; Güngör, Cenap.
In: MOL CANCER RES, Vol. 12, No. 5, 01.05.2014, p. 670-80.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer
AU - Rawnaq, Tamina
AU - Dietrich, Luisa
AU - Wolters-Eisfeld, Gerrit
AU - Uzunoglu, Faik G
AU - Vashist, Yogesh K
AU - Bachmann, Kai
AU - Simon, Ronald
AU - Izbicki, Jakob R
AU - Bockhorn, Maximilian
AU - Güngör, Cenap
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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-α and EGF being the main inductors of MK expression in PDAC. Implications: This study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC and therefore defines an attractive new therapeutic target in pancreatic cancer. Mol Cancer Res; 12(5); 670-80. ©2014 AACR.
AB - 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-α and EGF being the main inductors of MK expression in PDAC. Implications: This study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC and therefore defines an attractive new therapeutic target in pancreatic cancer. Mol Cancer Res; 12(5); 670-80. ©2014 AACR.
U2 - 10.1158/1541-7786.MCR-13-0467
DO - 10.1158/1541-7786.MCR-13-0467
M3 - SCORING: Journal article
C2 - 24567526
VL - 12
SP - 670
EP - 680
JO - MOL CANCER RES
JF - MOL CANCER RES
SN - 1541-7786
IS - 5
ER -