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
February 2013 Volume 29 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
February 2013 Volume 29 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

Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models

  • Authors:
    • Guo-Cai Li
    • Qing-Hai Ye
    • Qiong-Zhu Dong
    • Ning Ren
    • Hu-Liang Jia
    • Lun-Xiu Qin
  • View Affiliations / Copyright

    Affiliations: Liver Cancer Institute and Zhongshan Hospital, Institute of Biomedical Science, Fudan University, Shanghai, P.R. China
  • Pages: 713-719
    |
    Published online on: December 10, 2012
       https://doi.org/10.3892/or.2012.2174
  • 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

Mesenchymal stem cells (MSCs) can have an effect on the growth and metastasis of human malignancies, including hepatocellular carcinoma (HCC); however, their mechanisms of action are not yet fully understood. The cell fusion of stem cell derived from bone marrow with other cells has been increasingly emphasized. The purpose of this study was to investigate the distribution of MSCs in mouse models of HCC, as well as the cell fusion between MSCs and HCC cells. We labeled HCC cells and MSCs with green fluorescence protein (GFP), red fluorescence protein (RFP), 4',6-diamidino-2-phenylindole (DAPI) and 5-bromo-2'-deoxyuridine (BrdU). We found that MSCs fused with HCC cells at a low frequency in vitro. MSCs were found to be merged into HCC tissues after intravenous injection, and compared with the mice not injected with MSCs, the MSCs were mainly distributed in the tumor stroma; Following the injection of the MSCs, the tumor stroma was found to have expanded in size, and the rate of pulmonary metastasis in the MSC-injected group was significantly lower (20%) compared to that in the group not injected with MSCs (100%, P=0.01). These data suggest that cell fusion between MSCs and HCC after engraftment is not one of the main mechanisms of action of the MSCs, while stromal differentiation is a major mechanism of action of the MSCs, leading to the inhibition of the pulmonary metastasis of HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M and Bekele BN: Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst. 96:1593–1603. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL and Neel M: Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 5:309–313. 1999. View Article : Google Scholar : PubMed/NCBI

3 

Beachy PA, Karhadkar SS and Berman DM: Tissue repair and stem cell renewal in carcinogenesis. Nature. 432:324–331. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Fierro FA, Sierralta WD, Epuñan MJ and Minguell JJ: Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination. Clin Exp Metastas. 21:313–319. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C and Chen Y: Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 80:267–274. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R and Weinberg RA: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449:557–563. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Reyes M, Dudek A, Jahagirdan B, Koodie L, Marker PH and Verfaillie CM: Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 109:337–346. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noël D and Jorgensen C: Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 102:3837–3844. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Portolani N, Coniglio A, Ghidoni S, GiovanellMi A, Benetti G and Tiberio A: Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 243:229–235. 2006. View Article : Google Scholar

10 

Ye QH, Qin LX, Forgues M, He P, Kim JW and Peng AC: Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med. 9:416–423. 2003. View Article : Google Scholar

11 

Alison MR and Lovell MJ: Liver cancer: the role of stem cells. Cell Prolif. 38:407–421. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Vassilopoulos G, Wang PR and Russell DW: Transplanted bone marrow regenerates liver by cell fusion. Nature. 422:901–904. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S and Grompe M: Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 422:897–901. 2003.PubMed/NCBI

14 

Li GC, Ye QH, Xue YH, Sun HJ, Zhou HJ, Ren N, Jia HL, Shi J, Wu JC, Dai C, Dong QZ and Qin LX: Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97-H cell line. Cancer Sci. 101:2546–2553. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Nygren JM, Jovinge S, Breitbach M, Säwén P, Röll W, Hescheler J, Taneera J, Fleischmann BK and Jacobsen SE: Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med. 10:494–501. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Chen EH, Grote E, Mohler W and Vignery A: Cell-cell fusion. FEBS Lett. 581:2181–2193. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Ying QL, Nichols J, Chambers I and Smith A: BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell. 115:281–292. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Li Y, Tang Y, Ye L, Liu B, Liu K and Chen J: Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol. 129:43–51. 2003.

19 

Li Y, Tang ZY, Ye SL, Liu YK, Chen J and Xue Q: Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol. 7:630–636. 2001.PubMed/NCBI

20 

Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Matsuura A, Hamada H and Niitsu Y: Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood. 106:756–763. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Kozorovitskiy Y and Gould E: Stem cell fusion in the brain. Nat Cell Biol. 5:952–954. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Wang X, Willenbring H and Akkari Y: Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 42:2897–2901. 2003.

23 

Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ and Alvarez-Buylla A: Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 425:968–973. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Menthena A, Deb N, Oertel M, Grozdanov PN, Sandhu J, Shah S, Guha C, Shafritz DA and Dabeva MD: Bone marrow progenitors are not the source of expanding oval cells in injured liver. Stem Cells. 22:1049–1061. 2004.PubMed/NCBI

25 

Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, Daniel DM, Ruggero D and Shmelkov SV: VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 438:820–827. 2005. View Article : Google Scholar

26 

Ball SG, Shuttleworth AC and Kielty CM: Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol. 36:598–606. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Iakova P, Awad SS and Timchenko NA: Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell. 113:495–506. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Wagemaker G, Neelis KJ and Wognum AW: Surface markers and growth factor receptors of immature hemopoie tic stem cell subsets. Stem Cells. 13(Suppl 1): 165–171. 1995.PubMed/NCBI

29 

Zheng YW and Taniguchi H: Diversity of hepatic stem cells in the fetal and adult liver. Semin Liver Dis. 23:337–348. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Goldsborough MD, Tilkins ML, Price PJ, Lobo-Alfonso J, Morrison JR and Stevens ME: Serum-free culture of murine embryonic stem (ES) cells. Focus. 20:8–12. 1998.

31 

Desmouliere A, Guyot C and Gabbiani G: The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 48:509–517. 2004. View Article : Google Scholar : PubMed/NCBI

32 

De Wever O and Mareel M: Role of tissue stroma in cancer cell invasion. J Pathol. 200:429–447. 2003.PubMed/NCBI

33 

Direkze NC and Alison MR: Bone marrow and tumour stroma: an intimate relationship. Hematol Oncol. 24:189–195. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Littlepage LE, Egeblad M and Werb Z: Coevolution of cancer and stromal cellular responses. Cancer Cell. 7:499–500. 2005. View Article : Google Scholar : PubMed/NCBI

35 

Welm AL: TGFbeta primes breast tumor cells for metastasis. Cell. 33:27–28. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li G, Ye Q, Dong Q, Ren N, Jia H and Qin L: Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models. Oncol Rep 29: 713-719, 2013.
APA
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., & Qin, L. (2013). Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models. Oncology Reports, 29, 713-719. https://doi.org/10.3892/or.2012.2174
MLA
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., Qin, L."Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models". Oncology Reports 29.2 (2013): 713-719.
Chicago
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., Qin, L."Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models". Oncology Reports 29, no. 2 (2013): 713-719. https://doi.org/10.3892/or.2012.2174
Copy and paste a formatted citation
x
Spandidos Publications style
Li G, Ye Q, Dong Q, Ren N, Jia H and Qin L: Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models. Oncol Rep 29: 713-719, 2013.
APA
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., & Qin, L. (2013). Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models. Oncology Reports, 29, 713-719. https://doi.org/10.3892/or.2012.2174
MLA
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., Qin, L."Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models". Oncology Reports 29.2 (2013): 713-719.
Chicago
Li, G., Ye, Q., Dong, Q., Ren, N., Jia, H., Qin, L."Mesenchymal stem cells seldomly fuse with hepatocellular carcinoma cells and are mainly distributed in the tumor stroma in mouse models". Oncology Reports 29, no. 2 (2013): 713-719. https://doi.org/10.3892/or.2012.2174
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