Oncotarget

Research Papers:

Emerging role of LOXL2 in the promotion of pancreas cancer metastasis

Joon Seong Park, Ji-hae Lee, Yun Sun Lee, Jae Keun Kim, Seung Myung Dong and Dong Sup Yoon _

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Oncotarget. 2016; 7:42539-42552. https://doi.org/10.18632/oncotarget.9918

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Abstract

Joon Seong Park1, Ji-hae Lee2, Yun Sun Lee1, Jae Keun Kim1, Seung Myung Dong2, Dong Sup Yoon1

1Pancreatobiliary Cancer Clinic, Department of Surgery, Gangnam Severance Hospital, Yonsei University, Seoul, Korea

2Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea

Correspondence to:

Seung Myung Dong, email: smdong@ncc.re.kr

Dong Sup Yoon, email: yds6110@yuhs.ac

Keywords: pancreas cancer, metastasis, EMT, LOXL2, prognosis

Received: November 11, 2015     Accepted: May 04, 2016     Published: June 07, 2016

ABSTRACT

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in cancer. We analyzed the prognostic impact of LOXL2 in pancreatic cancer patients and investigated the role of LOXL2 in pancreatic cancer cell lines. Immunohistochemical analysis was performed in samples from 80 patients and showed LOXL2 expression in 81.2% of patients with pancreatic cancer. Regarding recurrence patterns, LOXL2-positive tumors showed a significantly higher rate of distant recurrence. The 1-year and 3-year disease-free survival rates were 84.6% and 0.0%, respectively, for LOXL2-negative patients, and 27.8 % and 0.0 %, respectively, for LOXL2-positive patients. On univariate analysis, combined resection of major vessels, depth of invasion, tumor stage, and LOXL2- positive status were significant factors for poor prognosis. After identification of LOXL2 expression in pancreatic cancer cell lines, LOXL2-silenced and LOXL2-overexpressed cell lines were used to perform transwell invasion and transendothelial migration assays.

In vitro studies indicated that LOXL2 silencing in MIA PaCa-2 and PANC-1 cells induced a mesenchymal–epithelial transition (MET)-like process associated with decreased invasive and migratory properties. LOXL2 overexpression in AsPC-1 and BxPC-3 cells enhanced the epithelial-mesenchymal transition (EMT)-like process and increased migratory and invasive activity. These clinical and preclinical data confirm that higher LOXL2 expression is associated with the invasiveness of pancreatic cancer cells and the low survival rate of pancreatic cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in pancreatic cancer.


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