Jie Zhang1,2,3, Lei Zhang4, Can Li1,2, Caiting Yang1,2, Lili Li1,2, Shushu Song1,2, Hao Wu1,2, Fenglin Liu5, Lan Wang6,7, Jianxin Gu1,2,3. 1. Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. 2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, People's Republic of China. 3. Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. 4. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 20032, People's Republic of China. 5. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 20032, People's Republic of China. Liu.fenglin@zs-hospital.sh.cn. 6. Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People's Republic of China. wanglan1102@yahoo.com. 7. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, People's Republic of China. wanglan1102@yahoo.com.
Abstract
PURPOSE: Pancreatic cancer (PC) is an aggressive type of cancer that exhibits a rapid progression. Previously LOX-1, which is a type II trans-membrane glycoprotein that is expressed in endothelial cells, has been found to be involved in the development of several types of cancer. As yet, however, the expression of LOX-1 and its functional consequences in PC have not been documented. The present study was aimed at investigating the prognostic relevance of LOX-1 expression in PC patients and at resolving its role in PC metastasis. METHODS: LOX-1 expression was assessed by immunohistochemistry on a tissue microarray containing samples from 98 PC patients. Kaplan-Meier analyses were performed to compare survival curves, whereas Cox regression analyses were performed to explore the independent prognostic value of LOX-1 expression on the overall survival (OS) of PC patients. Harrel's concordance index was applied to calculate the predictive accuracy of established models. In addition, in vitro scratch wound healing and Transwell assays were used to assess the effect of LOX-1 expression silencing and over-expression on PC cell migration and invasion, whereas Cell Counting Kit-8 (CCK8) and Flow Cytometry (FCM) assays were used to assess its effects on PC cell proliferation and apoptosis. RESULTS: We found that LOX-1 is highly expressed in the PC tumor tissues tested and is related to the occurrence of lymph node metastases, higher TNM stages and a poor OS. We also found that LOX-1 expression may serve as an independent prognostic factor for the OS of PC patients. Our in vitro assays revealed that LOX-1 expression may promote the migration and invasion of PC cells through epithelial-mesenchymal transition (EMT). No effect on PC cell proliferation was noted. CONCLUSIONS: From our data we conclude that a high LOX-1 expression in PC tissues is indicative for the occurrence of lymph node metastases, high TNM stages and a poor prognosis. LOX-1 may serve as an independent prognostic biomarker. Our in vitro assays additionally revealed that LOX-1 may enhance the migration and invasion of PC cells through EMT. LOX-1 may also serve as a novel therapeutic target.
PURPOSE:Pancreatic cancer (PC) is an aggressive type of cancer that exhibits a rapid progression. Previously LOX-1, which is a type II trans-membrane glycoprotein that is expressed in endothelial cells, has been found to be involved in the development of several types of cancer. As yet, however, the expression of LOX-1 and its functional consequences in PC have not been documented. The present study was aimed at investigating the prognostic relevance of LOX-1 expression in PC patients and at resolving its role in PC metastasis. METHODS:LOX-1 expression was assessed by immunohistochemistry on a tissue microarray containing samples from 98 PC patients. Kaplan-Meier analyses were performed to compare survival curves, whereas Cox regression analyses were performed to explore the independent prognostic value of LOX-1 expression on the overall survival (OS) of PC patients. Harrel's concordance index was applied to calculate the predictive accuracy of established models. In addition, in vitro scratch wound healing and Transwell assays were used to assess the effect of LOX-1 expression silencing and over-expression on PC cell migration and invasion, whereas Cell Counting Kit-8 (CCK8) and Flow Cytometry (FCM) assays were used to assess its effects on PC cell proliferation and apoptosis. RESULTS: We found that LOX-1 is highly expressed in the PC tumor tissues tested and is related to the occurrence of lymph node metastases, higher TNM stages and a poor OS. We also found that LOX-1 expression may serve as an independent prognostic factor for the OS of PC patients. Our in vitro assays revealed that LOX-1 expression may promote the migration and invasion of PC cells through epithelial-mesenchymal transition (EMT). No effect on PC cell proliferation was noted. CONCLUSIONS: From our data we conclude that a high LOX-1 expression in PC tissues is indicative for the occurrence of lymph node metastases, high TNM stages and a poor prognosis. LOX-1 may serve as an independent prognostic biomarker. Our in vitro assays additionally revealed that LOX-1 may enhance the migration and invasion of PC cells through EMT. LOX-1 may also serve as a novel therapeutic target.
Authors: Z von Marschall; T Cramer; M Höcker; R Burde; T Plath; M Schirner; R Heidenreich; G Breier; E O Riecken; B Wiedenmann; S Rosewicz Journal: Gastroenterology Date: 2000-11 Impact factor: 22.682
Authors: Yaqing Zhang; Wei Yan; Meredith A Collins; Filip Bednar; Sabita Rakshit; Bruce R Zetter; Ben Z Stanger; Ivy Chung; Andrew D Rhim; Marina Pasca di Magliano Journal: Cancer Res Date: 2013-10-04 Impact factor: 12.701