title: STAT5b as molecular target in pancreatic cancer--inhibition of tumor growth, angiogenesis, and metastases.
abstract: The prognosis of patients suffering from pancreatic cancer is still poor and novel therapeutic options are urgently needed. Recently, the transcription factor signal transducer and activator of transcription 5b (STAT5b) was associated with tumor progression in human solid cancer. Hence, we assessed whether STAT5b might serve as an anticancer target in ductal pancreatic adenocarcinoma (DPAC). We found that nuclear expression of STAT5b can be detected in approximately 50% of DPAC. Blockade of STAT5b by stable shRNA-mediated knockdown showed no effects on tumor cell growth in vitro. However, inhibition of tumor cell motility was found even in response to stimulation with epidermal growth factor or interleukin-6. These findings were paralleled by a reduction of prometastatic and proangiogenic factors in vitro. Subsequent in vivo experiments revealed a strong growth inhibition on STAT5b blockade in subcutaneous and orthotopic models. These findings were paralleled by impaired tumor angiogenesis in vivo. In contrast to the subcutaneous model, the orthotopic model revealed a strong reduction of tumor cell proliferation that emphasizes the meaning of assessing targets in an appropriate microenvironment. Taken together, our results suggest that STAT5b might be a potential novel target for human DPAC.
authors.affiliation: Department of Surgery, University of Regensburg Medical Center, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehmert
authors.forename: Hedwig
authors.initials: H
authors.lastname: Schenk
authors.forename: Marina P
authors.initials: MP
authors.lastname: Kreutz
authors.forename: Maria E
authors.initials: ME
authors.lastname: Mycielska
authors.forename: Christina
authors.initials: C
authors.lastname: Hackl
authors.forename: Alexander
authors.initials: A
authors.lastname: Kroemer
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Schnitzbauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Stoeltzing
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Sven A
authors.initials: SA
authors.lastname: Lang
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D002291:Carcinoma, Papillary / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human