title: The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Authors' Affiliations: Department of General, Visceral and Thoracic Surgery, Experimental Oncology and 2Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tamina
authors.initials: T
authors.lastname: Rawnaq
authors.forename: Luisa
authors.initials: L
authors.lastname: Dietrich
authors.forename: Gerrit
authors.initials: G
authors.lastname: Wolters-Eisfeld
authors.forename: Faik G
authors.initials: FG
authors.lastname: Uzunoglu
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.forename: Kai
authors.initials: K
authors.lastname: Bachmann
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Cenap
authors.initials: C
authors.lastname: Güngör
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection
chemical_list: C066254:MDK protein, human; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D000078792:Midkine