Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2009

01-09-2009 | Gastrointestinal Oncology

Expression of Lysyl Oxidase Is Correlated with Lymph Node Metastasis and Poor Prognosis in Esophageal Squamous Cell Carcinoma

Authors: Makoto Sakai, MD, Hiroyuki Kato, MD, PhD, Akihiko Sano, MD, Naritaka Tanaka, MD, Takanori Inose, MD, Hitoshi Kimura, MD, PhD, Makoto Sohda, MD, PhD, Masanobu Nakajima, MD, PhD, Hiroyuki Kuwano, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2009

Login to get access

Abstract

Background

Lysyl oxidase (LOX), an extracellular matrix-remodeling enzyme, has been reported to regulate tumor metastasis. We investigated the clinical significance of LOX expression in esophageal squamous cell carcinoma (ESCC).

Methods

We examined LOX expression in ESCC cell lines by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We also examined LOX expression by real-time RT-PCR in 39 surgically resected ESCC and by immunohistochemistry in 122 surgically resected ESCC.

Results

LOX messenger RNA (mRNA) was expressed at a high level in TTn (originating from an ESCC metastatic lesion); at a moderate level in TE-2 and TE-15; and at a low level in TE-1, TE-8, and TE-13. In Western blotting, all cell lines expressed the catalytically inactive 50-kDa LOX at approximately the same levels, but catalytically active 32-kDa LOX was overexpressed only in TTn. LOX mRNA levels in ESCC tissues were significantly higher than those observed in normal esophageal tissues (P < 0.001) and had no significant correlation with tumor–node–metastasis (TNM) factors. High LOX protein expression had a significant correlation with presence of lymph node metastasis (P = 0.009) and number of lymph node metastases (P = 0.047). Overall and cancer-specific survival rates of patients with ESCC with high LOX expression were significantly lower than those of patients with ESCC with low LOX expression (P = 0.024 and P = 0.012). Univariate and multivariate analyses revealed that high LOX protein expression was an independent prognostic factor for ESCC.

Conclusions

Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.
Literature
1.
Kato H, Fukuchi M, Miyazaki T, et al. Surgical treatment for esophageal cancer. Current issues. Dig Surg. 2007; 24:88–95.PubMedCrossRef
2.
Isono K, Sato H, Nakayama K. Results of a nationwide study on the three-field lymph node dissection of esophageal cancer. Oncology. 1991;48:411–20.PubMedCrossRef
3.
Akiyama H, Tsurumaru M, Udagawa H, Kajiyama Y. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 1994;220:364–72.PubMedCrossRef
4.
Pinnell SR, Martin GR. The cross-linking of collagen and elastin: enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone. Proc Natl Acad Sci USA. 1968;61:708–16.PubMedCrossRef
5.
Smith-Mungo LI, Kagan HM. Lysyl oxidase: properties, regulation and multiple functions in biology. Matrix Biol. 1998;16:387–98.PubMedCrossRef
6.
Csiszar K. Lysyl oxidases: a novel multifunctional amine oxidase family. Prog Nucleic Acid Res Mol Biol. 2001;70:1–32.PubMedCrossRef
7.
Kagan HM, Li W. Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem. 2003;88:660–72.PubMedCrossRef
8.
Molnar J, Fong KS, He QP, et al. Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Biochim Biophys Acta. 2003;1647:220–4.PubMed
9.
Khakoo A, Thomas R, Trompeter R, Duffy P, Price R, Pope FM. Congenital cutis laxa and lysyl oxidase deficiency. Clin Genet. 1997;51:109–14.PubMed
10.
Royce PM, Camakaris J, Danks DM. Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes’ syndrome. Biochem J. 1980;192:579–86.PubMed
11.
Sibon I, Sommer P, Lamaziere JM, Bonnet J. Lysyl oxidase deficiency: a new cause of human arterial dissection. Heart. 2005;91:e33.PubMedCrossRef
12.
Kagan HM, Raghavan J, Hollander W. Changes in aortic lysyl oxidase activity in diet-induced atherosclerosis in the rabbit. Arteriosclerosis. 1981;1:287–91.PubMed
13.
Chanoki M, Ishii M, Kobayashi H, Fushida H, Yashiro N, Hamada T, et al. Increased expression of lysyl oxidase in skin with scleroderma. Br J Dermatol. 1995;133:710–5.PubMedCrossRef
14.
Kagan HM. Lysyl oxidase: mechanism, regulation and relationship to liver fibrosis. Pathol Res Pract. 1994;190:910–9.PubMed
15.
Payne SL, Fogelgren B, Hess AR, et al. Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism. Cancer Res. 2005;65:11429–36.PubMedCrossRef
16.
Erler JT, Bennewith KL, Nicolau M, et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 2006;440:1222–6.PubMedCrossRef
17.
Kirschmann DA, Seftor EA, Fong SF, et al. A molecular role for lysyl oxidase in breast cancer invasion. Cancer Res. 2002;62:4478–83.PubMed
18.
Bouez C, Reynaud C, Noblesse E, et al. The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model. Clin Cancer Res. 2006;12:1463–9.PubMedCrossRef
19.
Kaneda A, Wakazono K, Tsukamoto T, et al. Lysyl oxidase is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in human gastric cancers. Cancer Res. 2004;64:6410–5.PubMedCrossRef
20.
Lapointe J, Li C, Higgins JP, et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA. 2004;101:811–6.PubMedCrossRef
21.
Stassar MJ, Devitt G, Brosius M, et al. Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001;85:1372–82.PubMedCrossRef
22.
Kimura H, Kato H, Faried A, et al. Prognostic significance of EpCAM expression in human esophageal cancer. Int J Oncol. 2007;30:171–9.PubMed
23.
Kato H, Yoshikawa M, Miyazaki T, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma. Anticancer Res. 2002;22:3977–84.PubMed
24.
Fukai Y, Masuda N, Kato H, et al. Correlation between laminin-5 gamma2 chain and epidermal growth factor receptor expression in esophageal squamous cell carcinomas. Oncology. 2005;69:71–80.PubMedCrossRef
25.
Li PA, He Q, Cao T, et al. Up-regulation and altered distribution of lysyl oxidase in the central nervous system of mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Brain Res Mol Brain Res. 2004;120:115–22.PubMedCrossRef
26.
Narayanan AS, Siegel RC, Martin GR. On the inhibition of lysyl oxidase by -aminopropionitrile. Biochem Biophys Res Commun. 1972;46:745–51.PubMedCrossRef
27.
Uzel MI, Shih SD, Gross H, Kessler E, Gerstenfeld LC, Trackman PC. Molecular events that contribute to lysyl oxidase enzyme activity and insoluble collagen accumulation in osteosarcoma cell clones. J Bone Miner Res. 2000;15:1189–97.PubMedCrossRef
28.
Kaplan KB, Swedlow JR, Morgan DO, Varmus HE. c-Src enhances the spreading of src−/− fibroblasts on fibronectin by a kinase-independent mechanism. Genes Dev. 1995;9:1505–17.PubMedCrossRef
29.
Maung K, Easty DJ, Hill SP, Bennett DC. Requirement for focal adhesion kinase in tumor cell adhesion. Oncogene. 1999;18:6824–8.PubMedCrossRef
30.
Miyazaki T, Kato H, Nakajima M, et al. FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer. 2003;89:140–5.PubMedCrossRef
Metadata
Title
Expression of Lysyl Oxidase Is Correlated with Lymph Node Metastasis and Poor Prognosis in Esophageal Squamous Cell Carcinoma
Authors
Makoto Sakai, MD
Hiroyuki Kato, MD, PhD
Akihiko Sano, MD
Naritaka Tanaka, MD
Takanori Inose, MD
Hitoshi Kimura, MD, PhD
Makoto Sohda, MD, PhD
Masanobu Nakajima, MD, PhD
Hiroyuki Kuwano, MD, PhD
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0559-5

Other articles of this Issue 9/2009

Annals of Surgical Oncology 9/2009 Go to the issue

Controversies in the Management of Hepatic Colorectal Metastases

Controversies in the Management of Hepatic Colorectal Metastases

Endocrine Tumors

Charcoal Suspension Tattoo Localization for Differentiated Thyroid Cancer Recurrence

Breast Oncology

Response to Letter to the Editor: Isolated Tumor Cells in Sentinel Lymph Nodes and Clinical Implications for Early Breast Cancer

Endocrine Tumors

High Rate of Multifocality and Occult Lymph Node Metastases in Papillary Thyroid Carcinoma Arising in Thyroglossal Duct Cysts

Hepatobiliary and Pancreatic Tumors

The Impact of Obesity on Outcomes Following Pancreatectomy for Malignancy

Hepatobiliary and Pancreatic Tumors

Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: A Histological Assessment of 365 Patients in Japan