Han Chen1, Huan Peng2, Wenwu Liu3, Yanping Sun4, Ning Su4, Wentao Tang2, Xiaoli Zhang5, Jian Wang6, Long Cui2, Pingfang Hu6, Sheng Liu7. 1. Department of General Surgery, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China. 2. Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 3. Department of Diving Medicine, Second Military Medical University, Shanghai, China. 4. Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. 5. Department of Pathology, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China. 6. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China. 7. Department of General Surgery, Chinese People's Liberation Army No. 411 Hospital, Shanghai, China. Electronic address: liusheng196511@163.com.
Abstract
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is reported to be expressed in many cancer cell types and regarded as one of the most informative biochemical markers for poor prognosis. However, no previous study has evaluated whether PAI-1 could serve as a target in antitumor and antimetastasis therapies of colorectal cancer (CRC). METHODS: The plasma level of PAI-1 in CRC patients was detected and its correlation with the clinicopathologic features was evaluated. PAI-1 protein expression was assessed by Western blot assay and immunohistochemistry. The biologic consequences of PAI-1 silencing in colon cancer cell lines and CRC bearing nude mice were also investigated. RESULTS: Plasma PAI-1 level was higher in CRC patients with liver metastasis and correlated with liver metastasis, tumor size, differentiation, serosa infiltration, Duke's stage, and lymphatic metastasis. PAI-1 protein expression in the CRC tissue of patients with liver metastasis was significantly greater than that in those without liver metastasis. In addition, the abilities of proliferation, invasion, and migration of CRC cells transfected with lentivirus expressing PAI-1 small interfering RNA were reduced significantly. Nude mice inoculated with PAI-1 knockdown cells also had fewer metastatic nodules in the liver and smaller tumor volumes. CONCLUSION: Plasma PAI-1 level was increased in CRC patients with liver metastasis, and PAI-1 silencing may significantly compromise the malignant behaviors of CRC cells in vitro and in vivo. These findings may provide evidence for PAI-1 targeted therapy of CRC.
BACKGROUND:Plasminogen activator inhibitor-1 (PAI-1) is reported to be expressed in many cancer cell types and regarded as one of the most informative biochemical markers for poor prognosis. However, no previous study has evaluated whether PAI-1 could serve as a target in antitumor and antimetastasis therapies of colorectal cancer (CRC). METHODS: The plasma level of PAI-1 in CRC patients was detected and its correlation with the clinicopathologic features was evaluated. PAI-1 protein expression was assessed by Western blot assay and immunohistochemistry. The biologic consequences of PAI-1 silencing in colon cancer cell lines and CRC bearing nude mice were also investigated. RESULTS: Plasma PAI-1 level was higher in CRC patients with liver metastasis and correlated with liver metastasis, tumor size, differentiation, serosa infiltration, Duke's stage, and lymphatic metastasis. PAI-1 protein expression in the CRC tissue of patients with liver metastasis was significantly greater than that in those without liver metastasis. In addition, the abilities of proliferation, invasion, and migration of CRC cells transfected with lentivirus expressing PAI-1 small interfering RNA were reduced significantly. Nude mice inoculated with PAI-1 knockdown cells also had fewer metastatic nodules in the liver and smaller tumor volumes. CONCLUSION: Plasma PAI-1 level was increased in CRC patients with liver metastasis, and PAI-1 silencing may significantly compromise the malignant behaviors of CRC cells in vitro and in vivo. These findings may provide evidence for PAI-1 targeted therapy of CRC.
Authors: Richard Beatson; Virginia Tajadura-Ortega; Daniela Achkova; Gianfranco Picco; Theodora-Dorita Tsourouktsoglou; Sandra Klausing; Matthew Hillier; John Maher; Thomas Noll; Paul R Crocker; Joyce Taylor-Papadimitriou; Joy M Burchell Journal: Nat Immunol Date: 2016-09-05 Impact factor: 25.606
Authors: Bruno Märkl; Jochen Hardt; Simon Franz; Tina Schaller; Gerhard Schenkirsch; Bernadette Kriening; Reinhard Hoffmann; Stefan Rüth Journal: Gastroenterol Res Pract Date: 2017-02-12 Impact factor: 2.260