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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2016 Volume 14 Issue 2

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
August-2016 Volume 14 Issue 2

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

Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma

  • Authors:
    • Ji‑Zong Lin
    • Li‑Li Meng
    • Yan‑Zhu Li
    • Shu‑Xian Chen
    • Jian‑Liang Xu
    • Ya‑Jun Tang
    • Nan Lin
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Gynecology and Obstetrics, Sun Yat‑Sen Memorial Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510000, P.R. China
  • Pages: 1721-1725
    |
    Published online on: June 21, 2016
       https://doi.org/10.3892/mmr.2016.5418
  • 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

Previous studies have determined that activated hepatic stellate cells (aHSCs) promote the progression of hepatocellular carcinoma (HCC) by increasing angiogenesis in cancerous tissues. In addition, angiopoietin 1 (Ang‑1) has been reported to be involved in tumor growth and metastasis via the promotion of angiogenesis. It remains unclear whether aHSCs and Ang‑1 are involved in the angiogenesis in HCC. A total of 25 HCC and tumor‑adjacent tissues, and 21 normal liver tissues were used in the present study. Immunohistochemistry (IHC) was used to detect the expression of Ang‑1 and α smooth muscle actin (α‑SMA). The expression of CD34 was also analyzed using IHC to evaluate the microvessel density (MVD). The protein expression levels of Ang‑1 were evaluated using western blot analysis. The association between aHSC, Ang‑1 and angiogenesis was determined using Spearman's rank correlation coefficient. The present study determined that the expression of α‑SMA, Ang‑1 and MVD (CD34) was significantly higher in the HCC tissues when compared with tumor‑adjacent tissues and normal liver tissues. Spearman's rank analysis identified a positive correlation between the expression of α‑SMA, Ang‑1 and CD34. This suggests that α‑SMA‑positive aHSCs promoted angiogenesis by expressing Ang‑1, resulting in the proliferation and metastasis of HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

European Association For The Study Of The Liver1; European Organisation For Research And Treatment Of Cancer: EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 56:908–943. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Cao H, Phan H and Yang LX: Improved chemotherapy for hepatocellular carcinoma. Anticancer Res. 32:1379–1386. 2012.PubMed/NCBI

3 

El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Nordenstedt H, White DL and El-Serag HB: The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis. 42(Suppl 3): S206–S214. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Roxburgh P and Evans TR: Systemic therapy of hepatocellular carcinoma: Are we making progress? Adv Ther. 25:1089–1104. 2008. View Article : Google Scholar : PubMed/NCBI

6 

El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Fernández M, Semela D, Bruix J, Colle I, Pinzani M and Bosch J: Angiogenesis in liver disease. J Hepatol. 50:604–620. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Jia YL, Shi L, Zhou JN, Fu CJ, Chen L, Yuan HF, Wang YF, Yan XL, Xu YC, Zeng Q, et al: Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis. Hepatology. 54:1808–1818. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Sancho Bru P, Juez E, Moreno M, Khurdayan V, Morales-Ruiz M, Colmenero J, Arroyo V, Brenner DA, Ginés P and Bataller R: Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells. Liver Int. 30:31–41. 2010. View Article : Google Scholar

10 

Amann T, Bataille F, Spruss T, Mühlbauer M, Gäbele E, Schölmerich J, Kiefer P, Bosserhoff AK and Hellerbrand C: Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma. Cancer Sci. 100:646–653. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Olaso E, Salado C, Egilegor E, Gutierrez V, Santisteban A, Sancho-Bru P, Friedman SL and Vidal-Vanaclocha F: Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis. Hepatology. 37:674–685. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Holopainen T, Huang H, Chen C, Kim KE, Zhang L, Zhou F, Han W, Li C, Yu J, Wu J, et al: Angiopoietin-1 overexpression modulates vascular endothelium to facilitate tumor cell dissemination and metastasis establishment. Cancer Res. 69:4656–4664. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Ji Y, Wang Z, Li Z, Li K, Le X and Zhang T: Angiotensin II induces angiogenic factors production partly via AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells. Cell Physiol Biochem. 29:863–874. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Augustin HG, Koh GY, Thurston G and Alitalo K: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol. 10:165–177. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Huang H, Bhat A, Woodnutt G and Lappe R: Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer. 10:575–585. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Forbes SJ and Parola M: Liver fibrogenic cells. Best Pract Res Clin Gastroenterol. 25:207–217. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Taura K, De Minicis S, Seki E, Hatano E, Iwaisako K, Osterreicher CH, Kodama Y, Miura K, Ikai I, Uemoto S and Brenner DA: Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis. Gastroenterology. 135:1729–1738. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Wang XW, Cai CL, Xu JM, Jin H and Xu ZY: Increased expression of chitinase 3-like 1 is a prognosis marker for non-small cell lung cancer correlated with tumor angiogenesis. Tumour Biol. 36:901–907. 2015. View Article : Google Scholar

19 

Ding S, Li C, Lin S, Yang Y, Liu D, Han Y, Zhang Y, Li L, Zhou L and Kumar S: Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions. Hum Pathol. 37:861–866. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Sluimer JC and Daemen MJ: Novel concepts in atherogenesis: Angiogenesis and hypoxia in atherosclerosis. J Pathol. 218:7–29. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Gong Y, Sun X, Huo L, Wiley EL and Rao MS: Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology. 46:24–30. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Risau W: Mechanisms of angiogenesis. Nature. 386:671–674. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Wynn TA: Cellular and molecular mechanisms of fibrosis. J Pathol. 214:199–210. 2008. View Article : Google Scholar

24 

Sokolović A, Sokolović M, Boers W, Elferink RP and Bosma PJ: Insulin-like growth factor binding protein 5 enhances survival of LX2 human hepatic stellate cells. Fibrogenesis Tissue Repair. 3:32010. View Article : Google Scholar

25 

Stoeltzing O, Ahmad SA, Liu W, McCarty MF, Wey JS, Parikh AA, Fan F, Reinmuth N, Kawaguchi M, Bucana CD and Ellis LM: Angiopoietin-1 inhibits vascular permeability, angiogenesis, and growth of hepatic colon cancer tumors. Cancer Res. 63:3370–3377. 2003.PubMed/NCBI

26 

Thomas M and Augustin HG: The role of the Angiopoietins in vascular morphogenesis. Angiogenesis. 12:125–137. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Machein MR, Knedla A, Knoth R, Wagner S, Neuschl E and Plate KH: Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol. 165:1557–1570. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Valfrè di Bonzo L, Novo E, Cannito S, Busletta C, Paternostro C, Povero D and Parola M: Angiogenesis and liver fibrogenesis. Histol Histopathol. 24:1323–1341. 2009.PubMed/NCBI

29 

Medina J, Arroyo AG, Sánchez-Madrid F and Moreno-Otero R: Angiogenesis in chronic inflammatory liver disease. Hepatology. 39:1185–1195. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Novo E, Cannito S, Zamara E, Valfrè di Bonzo L, Caligiuri A, Cravanzola C, Compagnone A, Colombatto S, Marra F, Pinzani M and Parola M: Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol. 170:1942–1953. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lin JZ, Meng LL, Li YZ, Chen SX, Xu JL, Tang YJ and Lin N: Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma. Mol Med Rep 14: 1721-1725, 2016.
APA
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., & Lin, N. (2016). Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma. Molecular Medicine Reports, 14, 1721-1725. https://doi.org/10.3892/mmr.2016.5418
MLA
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., Lin, N."Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma". Molecular Medicine Reports 14.2 (2016): 1721-1725.
Chicago
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., Lin, N."Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma". Molecular Medicine Reports 14, no. 2 (2016): 1721-1725. https://doi.org/10.3892/mmr.2016.5418
Copy and paste a formatted citation
x
Spandidos Publications style
Lin JZ, Meng LL, Li YZ, Chen SX, Xu JL, Tang YJ and Lin N: Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma. Mol Med Rep 14: 1721-1725, 2016.
APA
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., & Lin, N. (2016). Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma. Molecular Medicine Reports, 14, 1721-1725. https://doi.org/10.3892/mmr.2016.5418
MLA
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., Lin, N."Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma". Molecular Medicine Reports 14.2 (2016): 1721-1725.
Chicago
Lin, J., Meng, L., Li, Y., Chen, S., Xu, J., Tang, Y., Lin, N."Importance of activated hepatic stellate cells and angiopoietin-1 in the pathogenesis of hepatocellular carcinoma". Molecular Medicine Reports 14, no. 2 (2016): 1721-1725. https://doi.org/10.3892/mmr.2016.5418
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