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Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer.

ABSTRACT: Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P?

SUBMITTER: Tanaka N

PROVIDER: S-EPMC6026164 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer.

Tanaka Nobutake N Yamada Suguru S Sonohara Fuminori F Suenaga Masaya M Hayashi Masamichi M Takami Hideki H Niwa Yukiko Y Hattori Norifumi N Iwata Naoki N Kanda Mitsuro M Tanaka Chie C Kobayashi Daisuke D Nakayama Goro G Koike Masahiko M Fujiwara Michitaka M Fujii Tsutomu T Kodera Yasuhiro Y

Scientific reports 20180629 1

Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher ...[more]

PMID: 29959362

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Project description:IntroductionLysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer.MethodsGene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 ((18)F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX.ResultsImmunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-NH2, was found to be localized in different cellular compartments under these conditions. After injection of [(18)F]fluorobenzoate-GGGDPKGGGGG-NH2, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer.ConclusionsThe present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer.

Dataset Information

Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer.

Publications

Clinical Implications of Lysyl Oxidase-Like Protein 2 Expression in Pancreatic Cancer.

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