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
November-2018 Volume 40 Issue 5

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
November-2018 Volume 40 Issue 5

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

C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer

  • Authors:
    • Huijin Li
    • Hui Li
    • Xiao‑Peng Li
    • Haojun Zou
    • Liting Liu
    • Wangqiao Liu
    • Tao Duan
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China, Department of Dermatology, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China, Shaanxi Normal University General Publishing House Co., Ltd., Xi'an, Shaanxi 710062, P.R. China, Department of Ophthalmology, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China
  • Pages: 2734-2741
    |
    Published online on: August 17, 2018
       https://doi.org/10.3892/or.2018.6660
  • 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

C‑C chemokine receptor type 2 (CCR2) is aberrantly expressed in a variety of tumor cells, and participates in the regulation of tumor cell progression, metastasis and immune escape. However, the mechanism of action of CCR2 in liver cancer remains unclear. In the present study, the aim was to elucidate the molecular mechanism underlying the regulation of epithelial‑to‑mesenchymal transition (EMT) by CCR2 in liver cancer cells. Initially, CCR2 expression in liver cancer tissues was measured, and the survival time of patients was analyzed by Kaplan‑Meier analysis. In liver cancer cells, the mRNA and protein expression levels of CCR2, matrix metalloproteinase‑2 (MMP2), E‑cadherin and vimentin were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell viability, migration and invasion were determined by Cell Counting Kit‑8, wound healing and Transwell chamber assays, respectively. Additionally, the binding between CCR2 and MMP2 was identified by co‑immunoprecipitation (Co‑IP). It was observed that CCR2 was abnormally upregulated in liver cancer tissues and significantly associated with the tumor diameter, metastasis and stage. The survival of patients with high CCR2 expression was lower compared with that of patients with low CCR2 expression. In addition, the number of cells that penetrated the transwell chamber membrane was significantly reduced following treatment with CCR2‑small interfering RNA (siRNA). Furthermore, CCR2 was found to participate in MMP2‑induced EMT, while CCR2‑siRNA transfection reduced the expression and activity of MMP2, and confirmed the specific binding between CCR2 and MMP2. Co‑IP also identified the independent interaction between endogenous proteins in HepG2 cells. These results revealed that CCR2 promotes EMT in liver cancer. Thus, CCR2 is an attractive novel target for inhibiting invasion and metastasis of liver cancer cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in china, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Jayachandran A, Dhungel B and Steel JC: Epithelial-to-mesenchymal plasticity of cancer stem cells: Therapeutic targets in hepatocellular carcinoma. J Hematol Oncol. 9:742016. View Article : Google Scholar : PubMed/NCBI

4 

Etik Ozer D, Suna N and Boyacioglu AS: Management of hepatocellular carcinoma: Prevention, surveillance, diagnosis, and staging. Exp Clin Transplant. 15:31–35. 2017.PubMed/NCBI

5 

Giannelli G, Koudelkova P, Dituri F and Mikulits W: Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 65:798–808. 2016. View Article : Google Scholar : PubMed/NCBI

6 

van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, Machat G, Grubinger M, Huber H and Mikulits W: Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 5:1169–1179. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Bottoni P, Isgro MA and Scatena R: The epithelialmesenchymal transition in cancer: A potential critical topic for translational proteomic research. Expert Rev Proteomics 13–115–133. 2016. View Article : Google Scholar

8 

Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C and Mukaida N: Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages and neovascularization. Int J Cancer. 118:335–345. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Zhang XW, Qin X, Qin CY, Yin YL, Chen Y and Zhu HL: Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance. Cancer Immunol Immunother. 62:563–570. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Akashi-Takamura S, Murakami M, Kijima H, Miyake K, Aburatani H and Maru Y: Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci. Nat Commu. 4:18532013. View Article : Google Scholar

11 

Zhuang H, Cao G, Kou C and Liu T: CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition in vitro through activation of the hedgehog pathway. Oncol Rep. 39:21–30. 2018.PubMed/NCBI

12 

Lim SY, Yuzhalin AE, Gordon-Weeks AN and Muschel RJ: Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget. 7:28697–28710. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Dutta R and Mahato RI: Recent advances in hepatocellular carcinoma therapy. Pharmacol Ther. 173:106–117. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Wong SHM, Fang CM, Chuah LH, Leong CO and Ngai SC: E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol. 121:11–22. 2018. View Article : Google Scholar : PubMed/NCBI

16 

Vu T and Datta PK: Regulation of EMT in colorectal cancer: A Culprit in metastasis. Cancers. 9:E1712017. View Article : Google Scholar : PubMed/NCBI

17 

Garg M: Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance. World J Stem Cells. 9:118–126. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Gaianigo N, Melisi D and Carbone C: EMT and treatment resistance in pancreatic cancer. Cancers. 9:E1222017. View Article : Google Scholar : PubMed/NCBI

19 

Qiu L, Tang Q, Li G and Chen K: Long non-coding RNAs as biomarkers and therapeutic targets recent insights into hepatocellular carcinoma. Life Sci. 191:273–282. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Giannelli G, Koudelkova P, Dituri F and Mikulits W: Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 65:798–808. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Hu J, Li X, Guo X, Guo Q, Xiang C, Zhang Z, Xing Y, Xi T and Zheng L: The CCR2 3′UTR functions as a competing endogenous RNA to inhibit breast cancer metastasis. J Cell Sci. 130:3399–3413. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Cai J, Wang M, Zhu M, Zhang Q, Zhang X, Yan Y, Qian H and Xu W: N-methyl-N-nitro-N'-nitrosoguanidine induces the expression of CCR2 in human gastric epithelial cells promoting CCL2-mediated migration. Mol Med Rep. 13:1083–1090. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Rao Q, Chen Y, Yeh CR, Ding J, Li L, Chang C and Yeh S: Recruited mast cells in the tumor microenvironment enhance bladder cancer metastasis via modulation of ERβ/CCL2/CCR2 EMT/MMP9 signals. Oncotarget. 7:7842–7855. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Moisan F, Francisco EB, Brozovic A, Duran GE, Wang YC, Chaturvedi S, Seetharam S, Snyder LA, Doshi P and Sikic BI: Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers. Mol Oncol. 8:1231–1239. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Izumi K, Fang LY, Mizokami A, Namiki M, Li L, Lin WJ and Chang C: Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Mol Med. 5:1383–1401. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li H, Li H, Li XP, Zou H, Liu L, Liu W and Duan T: C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer. Oncol Rep 40: 2734-2741, 2018.
APA
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., & Duan, T. (2018). C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer. Oncology Reports, 40, 2734-2741. https://doi.org/10.3892/or.2018.6660
MLA
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., Duan, T."C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer". Oncology Reports 40.5 (2018): 2734-2741.
Chicago
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., Duan, T."C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer". Oncology Reports 40, no. 5 (2018): 2734-2741. https://doi.org/10.3892/or.2018.6660
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Li H, Li XP, Zou H, Liu L, Liu W and Duan T: C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer. Oncol Rep 40: 2734-2741, 2018.
APA
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., & Duan, T. (2018). C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer. Oncology Reports, 40, 2734-2741. https://doi.org/10.3892/or.2018.6660
MLA
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., Duan, T."C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer". Oncology Reports 40.5 (2018): 2734-2741.
Chicago
Li, H., Li, H., Li, X., Zou, H., Liu, L., Liu, W., Duan, T."C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer". Oncology Reports 40, no. 5 (2018): 2734-2741. https://doi.org/10.3892/or.2018.6660
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