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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
July 2013 Volume 43 Issue 1

Full Size Image

Cover Legend PDF

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
July 2013 Volume 43 Issue 1

Full Size Image

Cover Legend PDF

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

Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas

  • Authors:
    • Manuela Salerno
    • Sofia Avnet
    • Gloria Bonuccelli
    • Adriana Eramo
    • Ruggero De Maria
    • Marco Gambarotti
    • Gabriella Gamberi
    • Nicola Baldini
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy, Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy, Regina Elena Cancer Institute, Rome, Italy, Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy
  • Pages: 95-102
    |
    Published online on: May 1, 2013
       https://doi.org/10.3892/ijo.2013.1927
  • 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

Musculoskeletal sarcomas are aggressive malignancies often characterized by an adverse prognosis despite the use of intense multiagent chemotherapy or molecular targeted therapy in combination to surgery and radiotherapy. Stem-like cells identified within solid tumors have been recently implicated in drug resistance, metastasis and local relapse. Here, we report the identification of putative cancer stem cells (CSCs) in sarcomas using a sphere culture system. These sarcospheres, able to grow in anchorage-independent and serum-starved conditions, express the pluripotent embryonic stem cell marker genes OCT3/4, Nanog and SOX2. Expression levels of these genes were greater in sarcospheres than in the parental tumor cultures. Importantly, the isolated tumor spheres transplanted into mice were tumorigenic and capable of recapitulating the human disease. Finally, we demonstrated that low (1%) O2 conditions, reproducing those found within the tumor microenvironment, significantly increase the number and the size of sarcospheres. The sphere formation assay is, therefore, a valuable method for the isolation of putative CSCs from human sarcomas and its efficiency is improved by controlling oxygen availability. This method provides a reliable preclinical model that can be used for future studies aimed at investigating crucial aspects of sarcoma biology, such as resistance to treatments and relapse.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1. 

Luis ÁM, Aguilar DP and Martín JA: Multidisciplinary management of soft tissue sarcomas. Clin Transl Oncol. 12:543–553. 2010.

2. 

Burningham Z, Hashibe M, Spector L and Schiffman JD: The epidemiology of sarcoma. Clin Sarcoma Res. 2:13–16. 2012. View Article : Google Scholar

3. 

Keedy VL: Treating metastatic soft-tissue or bone sarcomas - potential role of ridaforolimus. Onco Targets Ther. 5:153–160. 2012. View Article : Google Scholar : PubMed/NCBI

4. 

Lapidot T, Sirard C, Vormoor J, et al: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 17:645–648. 1994. View Article : Google Scholar : PubMed/NCBI

5. 

Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI

6. 

Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI

7. 

Jordan CT, Guzman ML and Noble M: Cancer stem cells. N Engl J Med. 355:1253–1261. 2006. View Article : Google Scholar : PubMed/NCBI

8. 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

9. 

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J and Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI

10. 

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI

11. 

Li C, Heidt DG, Dalerba P, et al: Identification of pancreatic cancer stem cells. Cancer Res. 67:1030–1037. 2007. View Article : Google Scholar : PubMed/NCBI

12. 

Schatton T, Murphy GF, Frank NY, et al: Identification of cells initiating human melanomas. Nature. 451:345–349. 2008. View Article : Google Scholar : PubMed/NCBI

13. 

Zhang S, Balch C, Chan MW, et al: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68:4311–4320. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Lang Sh, Frame F and Collins A: Prostate cancer stem cells. J Pathol. 217:299–306. 2009. View Article : Google Scholar : PubMed/NCBI

15. 

Ponti D, Costa A, Zaffaroni N, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI

16. 

Deleyrolle LP, Ericksson G, Morrison BJ, et al: Determination of somatic and cancer stem cell self-renewing symmetric division rate using sphere assays. PLoS One. 6:e158442011. View Article : Google Scholar : PubMed/NCBI

17. 

Liu T, Cheng W, Lai D, Huang Y and Guo L: Characterization of primary ovarian cancer cells in different culture systems. Oncol Rep. 23:1277–1284. 2010.PubMed/NCBI

18. 

Gibbs CP, Kukekov VG, Reith JD, et al: Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia. 7:967–976. 2005. View Article : Google Scholar : PubMed/NCBI

19. 

Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K and Takakura Y: Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines. Int J Oncol. 34:1381–1386. 2009.PubMed/NCBI

20. 

Wang L, Park P and Lin CY: Characterization of stem cell attributes in human osteosarcoma cell lines. Cancer Biol Ther. 8:543–552. 2009. View Article : Google Scholar : PubMed/NCBI

21. 

Rainusso N, Man TK, Lau CC, et al: Identification and gene expression profiling of tumor-initiating cells isolated from human osteosarcoma cell lines in an orthotopic mouse model. Cancer Biol Ther. 12:278–287. 2011. View Article : Google Scholar : PubMed/NCBI

22. 

Basu-Roy U, Seo E, Ramanathapuram L, et al: Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas. Oncogene. 31:2270–2282. 2012. View Article : Google Scholar : PubMed/NCBI

23. 

Suvà ML, Riggi N, Stehle JC, et al: Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res. 69:1776–1781. 2009.

24. 

Sette G, Salvati V, Memeo L, et al: EGFR inhibition abrogates leiomyosarcoma cell chemoresistance through inactivation of survival pathways and impairment of CSC potential. PLoS One. 7:e468912012. View Article : Google Scholar : PubMed/NCBI

25. 

Murase M, Kano M, Tsukahara T, et al: Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Br J Cancer. 101:1425–1432. 2009. View Article : Google Scholar : PubMed/NCBI

26. 

Lohberger B, Rinner B, Stuendl N, et al: Aldehyde dehydrogenase 1, a potential marker for cancer stem cells in human sarcoma. PLoS One. 7:e436642012. View Article : Google Scholar : PubMed/NCBI

27. 

Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB and Rich JN: Hypoxia inducible factors in cancer stem cells. Br J Cancer. 102:789–795. 2010. View Article : Google Scholar : PubMed/NCBI

28. 

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

29. 

Felipe Rico J, Hassane DC and Guzman ML: Acute myelogenous leukemia stem cells: from bench to bedside. Cancer Lett. Jun 17–2012.(Epub ahead of print).

30. 

Reynolds BA and Weiss S: Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 255:1707–1710. 1992. View Article : Google Scholar : PubMed/NCBI

31. 

Hallett RM, Kondratyev MK, Giacomelli AO, Nixon AM, Girgis-Gabardo A, Ilieva D and Hassell JA: Small molecule antagonists of the Wnt/β-catenin signaling pathway target breast tumor-initiating cells in a Her2/Neu mouse model of breast cancer. PLoS One. 7:e339762012.

32. 

Gibbs CP Jr, Levings PP and Ghivizzani SC: Evidence for the osteosarcoma stem cell. Curr Orthop Pract. 22:322–326. 2011. View Article : Google Scholar : PubMed/NCBI

33. 

Trucco M and Loeb D: Sarcoma stem cells: do we know what we are looking for? Sarcoma. 2012 291705:May 9–2012.(Epub ahead of print). View Article : Google Scholar

34. 

Galli R, Borello U, Gritti A, et al: Skeletal myogenic potential of human and mouse neural stem cells. Nat Neurosci. 3:986–991. 2000. View Article : Google Scholar : PubMed/NCBI

35. 

Toguchida J and Nakayama T: Molecular genetics of sarcomas: applications to diagnoses and therapy. Cancer Sci. 100:1573–1580. 2009. View Article : Google Scholar : PubMed/NCBI

36. 

Tolar J, Nauta AJ, Osborn MJ, et al: Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 25:371–379. 2007. View Article : Google Scholar : PubMed/NCBI

37. 

Tirino V, Desiderio V, Paino F, et al: Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo. FASEB J. 25:2022–2030. 2011. View Article : Google Scholar : PubMed/NCBI

38. 

Jiang X, Gwye Y, Russell D, et al: CD133 expression in chemo-resistant Ewing sarcoma cells. BMC Cancer. 10:116–127. 2012. View Article : Google Scholar : PubMed/NCBI

39. 

Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M and Kornblum HI: Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA. 100:15178–15183. 2003. View Article : Google Scholar : PubMed/NCBI

40. 

Gupta PB, Chaffer CL and Weinberg RA: Cancer stem cells: mirage or reality? Nat Med. 5:1010–1012. 2009. View Article : Google Scholar : PubMed/NCBI

41. 

Mohyeldin A, Garzón-Muvdi T and Quiñones-Hinojosa A: Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 7:150–161. 2010. View Article : Google Scholar : PubMed/NCBI

42. 

Rosová I, Dao M, Capoccia B, Link D and Nolta JA: Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 26:2173–2182. 2008.PubMed/NCBI

43. 

McCord AM, Jamal M, Shankavaram UT, Lang FF, Camphausen K and Tofilon PJ: Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res. 7:489–497. 2009. View Article : Google Scholar : PubMed/NCBI

44. 

Okita K, Ichisaka T and Yamanaka S: Generation of germline-competent induced pluripotent stem cells. Nature. 448:313–317. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Salerno M, Avnet S, Bonuccelli G, Eramo A, De Maria R, Gambarotti M, Gamberi G and Baldini N: Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas. Int J Oncol 43: 95-102, 2013.
APA
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M. ... Baldini, N. (2013). Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas. International Journal of Oncology, 43, 95-102. https://doi.org/10.3892/ijo.2013.1927
MLA
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M., Gamberi, G., Baldini, N."Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas". International Journal of Oncology 43.1 (2013): 95-102.
Chicago
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M., Gamberi, G., Baldini, N."Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas". International Journal of Oncology 43, no. 1 (2013): 95-102. https://doi.org/10.3892/ijo.2013.1927
Copy and paste a formatted citation
x
Spandidos Publications style
Salerno M, Avnet S, Bonuccelli G, Eramo A, De Maria R, Gambarotti M, Gamberi G and Baldini N: Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas. Int J Oncol 43: 95-102, 2013.
APA
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M. ... Baldini, N. (2013). Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas. International Journal of Oncology, 43, 95-102. https://doi.org/10.3892/ijo.2013.1927
MLA
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M., Gamberi, G., Baldini, N."Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas". International Journal of Oncology 43.1 (2013): 95-102.
Chicago
Salerno, M., Avnet, S., Bonuccelli, G., Eramo, A., De Maria, R., Gambarotti, M., Gamberi, G., Baldini, N."Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas". International Journal of Oncology 43, no. 1 (2013): 95-102. https://doi.org/10.3892/ijo.2013.1927
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