Skip to main content

Advertisement

Log in

Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization?

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

An Erratum to this article was published on 23 April 2016

Abstract

Objectives

Angiogenesis and neovascularisation plays a crucial role for tumorigenesis and tumor progression in head and neck squamous cell carcinoma (HNSCC). The aim of our study was to investigate the neovascularization capacity by endothelial progenitor cells (EPC) in tumor patient as a possible predictor for tumor progression and tumor stage.

Materials and methods

Therefore, we investigated the cell number and biologic activity by cell migration and colony-forming ability of EPC. Cells were isolated from the peripheral venous blood of 79 patients who suffer HNSCC in different stages of disease. Thirty-three healthy individuals served as the control group.

Results

Significantly increased biological activities were reflected by expression of the migration rate (1027 ± 1510) in comparison to the control group (632 ± 269) and the clonal potency measured by colony-forming unit (CFU) (tumor patients (19.7 ± 12.3) vs. control group (10.84 ± 4.8)). To determine whether or not EPC number can be used as a valid prognostic marker for clinical outcome of tumor patients, we furthermore compared a “high EPC-number-subgroup” (HI) with a “low EPC-number-subgroup” (LO) in a Kaplan-Meier survival curve. The HI-subgroup shows herein clearly a worse outcome.

Conclusions

Our findings indicate a possible pathway for EPC to play a critical role in the vasculogenesis and consequently in the progression of HNSCC.

Clinical Relevance.

Our findings could serve as possible predictors for the neovascularisation potential in HNSCC tumor patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kruger M, Pabst AM, Walter C, Sagheb K, Gunther C, Blatt S, et al. (2014) The prevalence of human papilloma virus (HPV) infections in oral squamous cell carcinomas: a retrospective analysis of 88 patients and literature overview. J Craniomaxillofac Surg 42(7):1506–1514

    Article  PubMed  Google Scholar 

  2. Bose P, Brockton NT, Dort JC (2013) Head and neck cancer: from anatomy to biology. Int J Cancer 133(9):2013–2023

    Article  PubMed  Google Scholar 

  3. Chai RC, Lambie D, Verma M, Punyadeera C. Current trends in the etiology and diagnosis of HPV-related head and neck cancers. Cancer medicine 2015

  4. Wu JY, Yi C, Chung HR, Wang DJ, Chang WC, SY L, et al. (2010) Potential biomarkers in saliva for oral squamous cell carcinoma. Oral Oncol 46(4):226–231

    Article  PubMed  Google Scholar 

  5. Ziebart T, Walenta S, Kunkel M, Reichert TE, Wagner W, Mueller-Klieser W (2011) Metabolic and proteomic differentials in head and neck squamous cell carcinomas and normal gingival tissue. J Cancer Res Clin Oncol 137(2):193–199

    Article  PubMed  Google Scholar 

  6. Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J (1972) Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136(2):261–276

    Article  PubMed  PubMed Central  Google Scholar 

  7. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82(1):4–6

    Article  PubMed  Google Scholar 

  8. Moccia F, Poletto V. May the remodeling of the Ca toolkit in endothelial progenitor cells derived from cancer patients suggest alternative targets for anti-angiogenic treatment? Biochim Biophys Acta. 2014.

  9. Baeriswyl V, Christofori G (2009) The angiogenic switch in carcinogenesis. Semin Cancer Biol 19(5):329–337

    Article  PubMed  Google Scholar 

  10. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  PubMed  Google Scholar 

  11. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, T L, et al. (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967

    Article  PubMed  Google Scholar 

  12. Moschetta M, Mishima Y, Sahin I, Manier S, Glavey S, Vacca A, et al. (2014) Role of endothelial progenitor cells in cancer progression. Biochim Biophys Acta 1846(1):26–39

    PubMed  Google Scholar 

  13. Balaji S, King A, Crombleholme TM, Keswani SG (2013) The role of endothelial progenitor cells in postnatal vasculogenesis: implications for therapeutic neovascularization and wound healing. Adv Wound Care 2(6):283–295

    Article  Google Scholar 

  14. Pabst AM, Kruger M, Ziebart T, Jacobs C, Walter C. Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial progenitor cells after bisphosphonate therapy in vitro. Clinical oral investigations. 2015.

  15. Ziebart T, Schnell A, Walter C, Kammerer PW, Pabst A, Lehmann KM, et al. (2013) Interactions between endothelial progenitor cells (EPC) and titanium implant surfaces. Clin Oral Investig 17(1):301–309

    Article  PubMed  Google Scholar 

  16. Kaur S, Bajwa P (2014) A ’tete-a tete’ between cancer stem cells and endothelial progenitor cells in tumor angiogenesis. Clin Transl Oncol 16(2):115–121

    Article  PubMed  Google Scholar 

  17. Ribatti D (2004) The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med 8(3):294–300

    Article  PubMed  Google Scholar 

  18. Brunner M, Thurnher D, Heiduschka G, Grasl M, Brostjan C, Erovic BM (2008) Elevated levels of circulating endothelial progenitor cells in head and neck cancer patients. J Surg Oncol 98(7):545–550

    Article  PubMed  Google Scholar 

  19. S3-Leitlinie Diagnostik und Therapie des Mundhöhlenkarzinoms [Internet]. Leitlinienprogramm Onkologie der AWMW, Deutschen Krebsgesellschaft e.V. und Deutschen Krebshilfe e.V. 2012 [cited 28.01.2015]. Available from: http://www.awmf.org/uploads/tx_szleitlinien/007_100OLl_S3_Mundh%C3%B6hlenkarzinom_122012-122015.pdf.

  20. Barnes LEJW, Reichart P, Sdransky D (2005) World Health Organization Classification of Tumors. Pathology and Genetics of Head and Neck Tumors. Lyon. IARC Press:2005

  21. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):e1–e7

    Article  PubMed  Google Scholar 

  22. Ziebart T, Ziebart J, Gauss L, Pabst A, Ackermann M, Smeets R, et al. (2013) Investigation of inhibitory effects on EPC-mediated neovascularization by different bisphosphonates for cancer therapy. Biosci Rep 1(5):719–722

    Google Scholar 

  23. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, et al. (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7(11):1194–1201

    Article  PubMed  Google Scholar 

  24. Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, EC G, et al. (2005) Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11(3):261–262

    Article  PubMed  Google Scholar 

  25. Fadini GP, Losordo D, Dimmeler S (2012) Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res 110(4):624–637

    Article  PubMed  PubMed Central  Google Scholar 

  26. Janic B, AS A (2010) The role and therapeutic potential of endothelial progenitor cells in tumor neovascularization. TheScientificWorldJOURNAL 10:1088–1099

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gao D, Nolan D, McDonnell K, Vahdat L, Benezra R, Altorki N, et al. (2009) Bone marrow-derived endothelial progenitor cells contribute to the angiogenic switch in tumor growth and metastatic progression. Biochim Biophys Acta 1796(1):33–40

    PubMed  PubMed Central  Google Scholar 

  28. Madonna R, De Caterina R. Circulating endothelial progenitor cells: do they live up to their name? Vascular pharmacology. 2015.

  29. Ge YZ, Wu R, Lu TZ, Xin H, Yu P, Zhao Y, et al. (2015) Circulating endothelial progenitor cell: a promising biomarker in clinical oncology. Med Oncol 32(1):332

    Article  PubMed  Google Scholar 

  30. Kim HK, Song KS, Kim HO, Chung JH, Lee KR, YJ L, et al. (2003) Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer. Cancer Lett 198(1):83–88

    Article  PubMed  Google Scholar 

  31. Nowak K, Rafat N, Belle S, Weiss C, Hanusch C, Hohenberger P, et al. (2010) Circulating endothelial progenitor cells are increased in human lung cancer and correlate with stage of disease. Eur J Cardiothorac Surg 37(4):758–763

    Article  PubMed  Google Scholar 

  32. Yang B, Gu W, Peng B, Xu Y, Liu M, Che J, et al. (2012) High level of circulating endothelial progenitor cells positively correlates with serum vascular endothelial growth factor in patients with renal cell carcinoma. J Urol 188(6):2055–2061

    Article  PubMed  Google Scholar 

  33. Ramcharan SK, Lip GY, Stonelake PS, Blann AD (2013) Angiogenin outperforms VEGF, EPCs and CECs in predicting Dukes’ and AJCC stage in colorectal cancer. Eur J Clin Investig 43(8):801–808

    Article  Google Scholar 

  34. DuBois SG, Stempak D, Wu B, Mokhtari RB, Nayar R, KA J, et al. (2012) Circulating endothelial cells and circulating endothelial precursor cells in patients with osteosarcoma. Pediatr Blood Cancer 58(2):181–184

    Article  PubMed  Google Scholar 

  35. George AL, Bangalore-Prakash P, Rajoria S, Suriano R, Shanmugam A, Mittelman A, et al. (2011) Endothelial progenitor cell biology in disease and tissue regeneration. J Hematol Oncol 4:24

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mobarrez F, Antoniewicz L, Bosson JA, Kuhl J, Pisetsky DS, Lundback M (2014) The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers. PLoS One 9(2):e90314

    Article  PubMed  PubMed Central  Google Scholar 

  37. Umemura T, Higashi Y (2008) Endothelial progenitor cells: therapeutic target for cardiovascular diseases. J Pharmacol Sci 108(1):1–6

    Article  PubMed  Google Scholar 

  38. Hristov M, Erl W, Weber PC (2003) Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 23(7):1185–1189

    Article  PubMed  Google Scholar 

  39. Ha XQ, Zhao M, Li XY, Peng JH, Dong JZ, Deng ZY, et al. (2014) Distribution of endothelial progenitor cells in tissues from patients with gastric cancer. Oncol lett 7(5):1695–1700

    PubMed  PubMed Central  Google Scholar 

  40. Zhu H, Shao Q, Sun X, Deng Z, Yuan X, D Y, et al. (2012) The mobilization, recruitment and contribution of bone marrow-derived endothelial progenitor cells to the tumor neovascularization occur at an early stage and throughout the entire process of hepatocellular carcinoma growth. Oncol Rep 28(4):1217–1224

    PubMed  Google Scholar 

  41. Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319(5860):195–198

    Article  PubMed  Google Scholar 

  42. Zhao Y, Yu P, Wu R, Ge Y, Wu J, Zhu J, et al. (2013) Renal cell carcinoma-adjacent tissues enhance mobilization and recruitment of endothelial progenitor cells to promote the invasion of the neoplasm. Biomed Pharmacother 67(7):643–649

    Article  PubMed  Google Scholar 

  43. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, et al. (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85(3):221–228

    Article  PubMed  Google Scholar 

  44. Bertelsen LB, Hagensen M, Busk M, Zhang R, Knudsen AS, Nielsen N, et al. (2014) In vivo bio-distribution and homing of endothelial outgrowth cells in a tumor model. Nucl Med Biol 41(10):848–855

    Article  PubMed  Google Scholar 

  45. Krenning G, van Luyn MJ, Harmsen MC (2009) Endothelial progenitor cell-based neovascularization: implications for therapy. Trends Mol Med 15(4):180–189

    Article  PubMed  Google Scholar 

  46. Shantsila E, Watson T, Tse HF, Lip GY (2007) Endothelial colony forming units: are they a reliable marker of endothelial progenitor cell numbers? Ann Med 39(6):474–479

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Ziebart.

Ethics declarations

Funding

The study was funded by Deutsche Forschungsgemeinschaft (DFG), GZ: ZI 1461/2–1 and foundation tumor research head and neck (Stiftung Tumorforschung Kopf-Hals), Wiesbaden, Germany.

Conflict of Interest

The authors of the article declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The local ethics committee (Landesärztekammer Rheinland-Pfalz) approved the following experiments (Ethikvotum 837.837.11 (7924)). This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00784-016-1833-0.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ziebart, T., Blatt, S., Günther, C. et al. Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization?. Clin Oral Invest 20, 2293–2300 (2016). https://doi.org/10.1007/s00784-016-1785-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-016-1785-4

Keywords

Navigation