STAT5b as Molecular Target in Pancreatic Cancer-Inhibition of Tumor Growth, Angiogenesis, and Metastases

Moser, Christian and Ruemmele, Petra and Gehmert, Sebastian and Schenk, Hedwig and Kreutz, Marina P. and Mycielska, Maria E. and Hackl, Christina and Kroemer, Alexander and Schnitzbauer, Andreas A. and Stoeltzing, Oliver and Schlitt, Hans J. and Geissler, Edward K. and Lang, Sven A. (2012) STAT5b as Molecular Target in Pancreatic Cancer-Inhibition of Tumor Growth, Angiogenesis, and Metastases. NEOPLASIA, 14 (10). 915-U61. ISSN 1476-5586,

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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. Neoplasia (2012) 14, 915-925

Item Type: Article
Uncontrolled Keywords: CELL-CYCLE ARREST; SIGNAL TRANSDUCER; PROSTATE-CANCER; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; IN-VITRO; EXPRESSION; ACTIVATION; INVASION; ADENOCARCINOMA;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 May 2020 07:19
Last Modified: 05 May 2020 07:19
URI: https://pred.uni-regensburg.de/id/eprint/17965

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