Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2015 Volume 34 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2015 Volume 34 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation

  • Authors:
    • Sung Ae Koh
    • Kyung Hee Lee
  • View Affiliations / Copyright

    Affiliations: Department of Hematology-Oncology, College of Medicine, Yeungnam University, Namgu, Daegu 705-703, Republic of Korea
  • Pages: 2179-2187
    |
    Published online on: August 10, 2015
       https://doi.org/10.3892/or.2015.4189
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Lipocalin 2 (LCN2) is a member of lipocalin family that binds and transports a small lipophilic ligand, sharing a highly conserved tertiary structure and can be found as a monomer, homodimer, heterodimer with matrix metalloproteinase 9 (MMP9). The high molecule LCN2/MMP9 complex was found in several cancer types. Yet, the mechanisms of regulation between LCN2 with MMP9 in tumorigenesis is unclear. The aims of the present study were to identify the function of LCN2 associated with MMP9 in gastric cancer growth and metastasis. First, we confirmed that the expression level of LCN2 and MMP9 was upregulated by hepatocyte growth factor (HGF). To identify the association pathway of HGF-induced LCN2, the cells were treated with PI3-kinase inhibitor (LY294002), or MEK inhibitor (PD098059), or p38 inhibitor (SB203580) and then analyzed using western blotting. The HGF-mediated LCN2 protein level was decreased with LY294002. Also, the HGF-mediated MMP9 was decreased with LY294002. The role for LCN2 with HGF mediated MMP9 was determined by knockdown of LCN2. LCN2-sh RNA cells showed a decreased level of HGF-mediated MMP9. The HGF-mediated LCN2 protein level was decreased with treatment of the NFκB inhibitor. We confirmed the role of HGF-mediated LCN2. HGF-mediated cell proliferation and in vitro invasion was decreased in LCN2 knockdown cell. In conclusion, the present study showed that LCN2 upregulated MMP9 through PI3K/AKT/NFκB pathway in gastric cancer. LCN2 has a role in cell proliferation and cell invasion in gastric cancer, which may be a possible target for developing gastric cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

Yang J and Moses MA: Lipocalin 2: A multifaceted modulator of human cancer. Cell Cycle. 8:2347–2352. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Xu S and Venge P: Lipocalins as biochemical markers of disease. Biochim Biophys Acta. 1482:298–307. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Alpízar-Alpízar W, Laerum OD, Illemann M, Ramírez JA, Arias A, Malespín-Bendaña W, Ramírez V, Lund LR, Borregaard N and Nielsen BS: Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori. Virchows Arch. 455:225–233. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Yan L, Borregaard N, Kjeldsen L and Moses MA: The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. J Biol Chem. 276:37258–37265. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Tschesche H, Zölzer V, Triebel S and Bartsch S: The human neutrophil lipocalin supports the allosteric activation of matrix metalloproteinases. Eur J Biochem. 268:1918–1928. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Sier CF, Kubben FJ, Ganesh S, Heerding MM, Griffioen G, Hanemaaijer R, van Krieken JH, Lamers CB and Verspaget HW: Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer. 74:413–417. 1996. View Article : Google Scholar : PubMed/NCBI

7 

Kubben FJ, Sier CF, van Duijn W, Griffioen G, Hanemaaijer R, van de Velde CJ, van Krieken JH, Lamers CB and Verspaget HW: Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer. Br J Cancer. 94:1035–1040. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Matsumura S, Oue N, Nakayama H, Kitadai Y, Yoshida K, Yamaguchi Y, Imai K, Nakachi K, Matsusaki K, Chayama K, et al: A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin Oncol. 131:19–25. 2005. View Article : Google Scholar

9 

Kjeldsen L, Johnsen AH, Sengeløv H and Borregaard N: Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 268:10425–10432. 1993.PubMed/NCBI

10 

Nuntagowat C, Leelawat K and Tohtong R: NGAL knockdown by siRNA in human cholangiocarcinoma cells suppressed invasion by reducing NGAL/MMP-9 complex formation. Clin Exp Metastasis. 27:295–305. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Fernández CA, Yan L, Louis G, Yang J, Kutok JL and Moses MA: The matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex plays a role in breast tumor growth and is present in the urine of breast cancer patients. Clin Cancer Res. 11:5390–5395. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, Feig B, Zhang W, Pusztai L, Symmans WF, et al: Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res. 69:8579–8584. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kubben FJ, Sier CF, Hawinkels LJ, Tschesche H, van Duijn W, Zuidwijk K, van der Reijden JJ, Hanemaaijer R, Griffioen G, Lamers CB, et al: Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer. Eur J Cancer. 43:1869–1876. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Yang SH, Kim JS, Oh TJ, Kim MS, Lee SW, Woo SK, Cho HS, Choi YH, Kim YH, Rha SY, et al: Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray. Int J Oncol. 22:741–750. 2003.PubMed/NCBI

15 

Parkin DM, Bray FI and Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer. 37(Suppl 8): S4–S66. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M and Kjeldsen L: Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut. 38:414–420. 1996. View Article : Google Scholar : PubMed/NCBI

18 

Rudd PM, Mattu TS, Masure S, Bratt T, Van den Steen PE, Wormald MR, Küster B, Harvey DJ, Borregaard N, Van Damme J, et al: Glycosylation of natural human neutrophil gelatinase B and neutrophil gelatinase B-associated lipocalin. Biochemistry. 38:13937–13950. 1999. View Article : Google Scholar : PubMed/NCBI

19 

Li SH, Hawthorne VS, Neal CL, Sanghera S, Xu J, Yang J, Guo H, Steeg PS and Yu D: Upregulation of neutrophil gelatinase-associated lipocalin by ErbB2 through nuclear factor-kappaB activation. Cancer Res. 69:9163–9168. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Liu Q and Nilsen-Hamilton M: Identification of a new acute phase protein. J Biol Chem. 270:22565–22570. 1995. View Article : Google Scholar : PubMed/NCBI

21 

Liu Q, Nilsen-Hamilton M and Xiong S: Synergistic regulation of the acute phase protein SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines. Sheng Li Xue Bao. 55:525–529. 2003.PubMed/NCBI

22 

Bauer M, Eickhoff JC, Gould MN, Mundhenke C, Maass N and Friedl A: Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat. 108:389–397. 2008. View Article : Google Scholar

23 

Tong Z, Kunnumakkara AB, Wang H, Matsuo Y, Diagaradjane P, Harikumar KB, Ramachandran V, Sung B, Chakraborty A, Bresalier RS, et al: Neutrophil gelatinase-associated lipocalin: A novel suppressor of invasion and angiogenesis in pancreatic cancer. Cancer Res. 68:6100–6108. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Viau A, El Karoui K, Laouari D, Burtin M, Nguyen C, Mori K, Pillebout E, Berger T, Mak TW, Knebelmann B, et al: Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest. 120:4065–4076. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Jiang W, Constante M and Santos MM: Anemia upregulates lipocalin 2 in the liver and serum. Blood Cells Mol Dis. 41:169–174. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF and Karin M: IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 118:285–296. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Li C and Chan YR: Lipocalin 2 regulation and its complex role in inflammation and cancer. Cytokine. 56:435–441. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Leng X, Wu Y and Arlinghaus RB: Relationships of lipocalin 2 with breast tumorigenesis and metastasis. J Cell Physiol. 226:309–314. 2011. View Article : Google Scholar

29 

Hanai J, Mammoto T, Seth P, Mori K, Karumanchi SA, Barasch J and Sukhatme VP: Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells. J Biol Chem. 280:13641–13647. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Lee HJ, Lee EK, Lee KJ, Hong SW, Yoon Y and Kim JS: Ectopic expression of neutrophil gelatinase-associated lipocalin suppresses the invasion and liver metastasis of colon cancer cells. Int J Cancer. 118:2490–2497. 2006. View Article : Google Scholar

31 

Zhang H, Xu L, Xiao D, Xie J, Zeng H, Wang Z, Zhang X, Niu Y, Shen Z, Shen J, et al: Upregulation of neutrophil gelatinase-associated lipocalin in oesophageal squamous cell carcinoma: Significant correlation with cell differentiation and tumour invasion. J Clin Pathol. 60:555–561. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Koh SA and Lee KH: HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation. Oncol Rep 34: 2179-2187, 2015.
APA
Koh, S.A., & Lee, K.H. (2015). HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation. Oncology Reports, 34, 2179-2187. https://doi.org/10.3892/or.2015.4189
MLA
Koh, S. A., Lee, K. H."HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation". Oncology Reports 34.4 (2015): 2179-2187.
Chicago
Koh, S. A., Lee, K. H."HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation". Oncology Reports 34, no. 4 (2015): 2179-2187. https://doi.org/10.3892/or.2015.4189
Copy and paste a formatted citation
x
Spandidos Publications style
Koh SA and Lee KH: HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation. Oncol Rep 34: 2179-2187, 2015.
APA
Koh, S.A., & Lee, K.H. (2015). HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation. Oncology Reports, 34, 2179-2187. https://doi.org/10.3892/or.2015.4189
MLA
Koh, S. A., Lee, K. H."HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation". Oncology Reports 34.4 (2015): 2179-2187.
Chicago
Koh, S. A., Lee, K. H."HGF mediated upregulation of lipocalin 2 regulates MMP9 through nuclear factor-κB activation". Oncology Reports 34, no. 4 (2015): 2179-2187. https://doi.org/10.3892/or.2015.4189
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team