Skip to main content

Advertisement

SpringerLink
Log in

TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is associated with tumor development and progression in a variety of epithelial carcinomas, while its expression and role in gliomas have not been considered. The aim of the study was to investigate TROP2 expression in malignant gliomas with different World Health Organization (WHO) classification and its correlation with tumor proliferation and angiogenesis. Immuohistochemistry was used to determine TROP2 and Ki-67 expression and microvessel density (MVD) in tumor specimens and normal brain tissues from 69 glioma patients and the relationship between TROP2 and Ki-67 and MVD was investigated. Immunohistochemistry results showed that the TROP2 expression was found in 59 (85.5 %) of the 69 tumor specimens, but no expression in normal brain tissues. Furthermore, TROP2 expression is significantly higher in WHO grade III (P = 0.025) and WHO grade IV (P = 0.011) gliomas than in WHO grade II gliomas. TROP2 expression correlates with Ki-67 (r = 0.676, P = 0.012) and MVD (r = 0.365, P = 0.035), but not with gender or age in human gliomas. These results suggested that the TROP2 correlated with malignancy, proliferation and angiogenesis in human gliomas. This is the first study describing TROP2 expression in gliomas and its proliferation and angiogenesis-related characteristic may serve as a potential therapeutic target for glioma treatment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS (2009) Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol 11:80–91

    Article  PubMed  CAS  Google Scholar 

  2. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  Google Scholar 

  3. Meyer MA (2008) Malignant gliomas in adults. N Engl J Med 359:1850

    PubMed  CAS  Google Scholar 

  4. Germano IM, Binello E (2009) Gene therapy as an adjuvant treatment for malignant gliomas: from bench to bedside. J Neurooncol 93:79–87

    Article  PubMed  CAS  Google Scholar 

  5. Lipinski M, Parks DR, Rouse RV, Herzenberg LA (1981) Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc Natl Acad Sci USA 78:5147–5150

    Article  PubMed  CAS  Google Scholar 

  6. Cubas R, Li M, Chen C, Yao Q (2009) Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta 1796:309–314

    PubMed  CAS  Google Scholar 

  7. Mühlmann G, Spizzo G, Gostner J, Zitt M, Maier H, Moser P, Gastl G, Zitt M, Müller HM, Margreiter R, Ofner D, Fong D (2009) TROP2 expression as prognostic marker for gastric carcinoma. J Clin Pathol 62:152–158

    Article  PubMed  Google Scholar 

  8. Fong D, Moser P, Krammel C, Gostner JM, Margreiter R, Mitterer M, Gastl G, Spizzo G (2008) High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer 99:1290–1295

    Article  PubMed  CAS  Google Scholar 

  9. Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063

    Article  PubMed  CAS  Google Scholar 

  10. Wang J, Day R, Dong Y, Weintraub SJ, Michel L (2008) Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers. Mol Cancer Ther 7:280–285

    Article  PubMed  CAS  Google Scholar 

  11. Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K (2008) TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186–191

    PubMed  CAS  Google Scholar 

  12. Cubas R, Zhang S, Li M, Chen C, Yao Q (2010) Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer 9:253

    Article  PubMed  Google Scholar 

  13. Trerotola M, Cantanelli P, Guerra E, Tripaldi R, Aloisi AL, Bonasera V, Lattanzio R, Lange RD, Weidle UH, Piantelli M, Alberti S (2012) Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. doi:10.1038/onc.2012.36

    Google Scholar 

  14. Mosolits S, Markovic K, Frodin JE, Virving L, Magnusson CG, Steinitz M, Fagerberg J, Mellstedt H (2004) Vaccination with Ep-CAM protein or anti-idiotypic antibody induces Th1-biased response against MHC class I- and II-restricted Ep-CAM epitopes in colorectal carcinoma patients. Clin Cancer Res 10:5391–5402

    Article  PubMed  CAS  Google Scholar 

  15. Raji R, Guzzo F, Carrara L, Varughese J, Cocco E, Bellone S, Betti M, Todeschini P, Gasparrini S, Ratner E, Silasi DA, Azodi M, Schwartz P, Rutherford TJ, Buza N, Pecorelli S, Santin AD (2011) Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody. J Exp Clin Cancer Res 30:106

    Article  PubMed  CAS  Google Scholar 

  16. Varughese J, Cocco E, Bellone S, de Leon M, Bellone M, Todeschini P, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD (2011) Uterine serous papillary carcinomas overexpress human trophoblast-cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized anti-Trop-2 monoclonal antibody. Cancer 117:3163–3172

    Article  PubMed  CAS  Google Scholar 

  17. Govindan SV, Stein R, Qu Z, Chen S, Andrews P, Ma H, Hansen HJ, Griffiths GL, Horak ID, Goldenberg DM (2004) Preclinical therapy of breast cancer with a radioiodinated humanized anti-EGP-1 monoclonal antibody: advantage of a residualizing iodine radiolabel. Breast Cancer Rea Treat 84:173–182

    Article  CAS  Google Scholar 

  18. Cea V, Sala C, Verpelli C (2012) Antiangiogenic therapy for glioma. J Signal Transduct 2012:483040

    PubMed  Google Scholar 

  19. Ralte AM, Sharma MC, Karak AK, Mehta VS, Sarkar C (2001) Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors. Pathol Oncol Res 7:267–278

    Article  PubMed  CAS  Google Scholar 

  20. Johannessen AL, Torp SH (2006) The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 12:143–147

    Article  PubMed  Google Scholar 

  21. Preusser M, Heinzl H, Gelpi E, Schonegger K, Haberler C, Birner P, Marosi C, Hegi M, Gorlia T, Hainfellner JA (2006) Histopathologic assessment of hot-spot microvessel density and vascular patterns in glioblastoma: poor observer agreement limits clinical utility as prognostic factors: a translational research project of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Cancer 107:162–170

    Article  PubMed  Google Scholar 

  22. Rahmah NN, Sakai K, Sano K, Hongo K (2012) Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions. J Neurooncol 107:559–564

    Article  PubMed  CAS  Google Scholar 

  23. Pang B, Fan H, Zhang IY, Liu B, Feng B, Meng L, Zhang R, Sadeghi S, Guo H, Pang Q (2012) HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis. J Neurooncol 106:543–549

    Article  PubMed  CAS  Google Scholar 

  24. Goldstein AS, Stoyanova T, Witte ON (2010) Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating cells and prostate cancer-initiating cells. Mol Oncol 4:385–396

    Article  PubMed  Google Scholar 

  25. Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF- κB as the matchmaker. Nat Immunol 12:715–723

    Article  PubMed  CAS  Google Scholar 

  26. Guerra E, Trerotola M, Dell’ Arciprete R, Bonasera V, Palombo B, El-Sewedy T, Ciccimarra T, Crescenzi C, Lorenzini F, Rossi C, Vacca G, Lattanzio R, Piantelli M, Alberti S (2008) A bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic mechanism in human cancer. Cancer Res 68:8113–8121

    Article  PubMed  CAS  Google Scholar 

  27. Stoyanova T, Goldstein AS, Cai H, Drake JM, Huang J, Witte ON (2012) Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via beta-catenin signaling. Genes Dev 26:2271–2285

    Article  PubMed  CAS  Google Scholar 

  28. Bello L, Giussani C, Carrabba G, Pluderi M, Costa F, Bikfalvi A (2004) Angiogenesis and invasion in gliomas. Cancer Treat Res 117:263–284

    Article  PubMed  CAS  Google Scholar 

  29. Leon SP, Folkerth RD, Black PM (1996) Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77:362–372

    Article  PubMed  CAS  Google Scholar 

  30. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  PubMed  CAS  Google Scholar 

  31. Ellis LM (2004) Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 18:1007–1021

    Article  PubMed  Google Scholar 

  32. Guo P, Hu B, Gu W, Xu L, Wang D, Huang HJ, Cavenee WK, Cheng SY (2003) Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. Am J Pathol 162:1083–1093

    Article  PubMed  CAS  Google Scholar 

  33. Chamberlain MC (2011) Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol 5:117–129

    Article  PubMed  CAS  Google Scholar 

  34. Shan YF, Huang YL, Xie YK, Tan YH, Chen BC, Zhou MT, Shi HQ, Yu ZP, Song QT, Zhang QY (2011) Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and alpha-fetoprotein expression status. Med Oncol 28:1012–1016

    Article  PubMed  CAS  Google Scholar 

  35. Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM (2011) Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 17:3157–3169

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Jianjun Xie for excellent technical assistance. This study was supported by the National Natural Science Foundation of China (Grant Nos. 30973109; 81100836; 81171062).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. School of Medicine, Shandong University, Jinan, People’s Republic of China

    Shanglei Ning

  2. Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China

    Nan Liang, Bin Liu, Xin Chen, Qi Pang & Tao Xin

Authors
  1. Shanglei Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qi Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tao Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qi Pang or Tao Xin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ning, S., Liang, N., Liu, B. et al. TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas. Neurol Sci 34, 1745–1750 (2013). https://doi.org/10.1007/s10072-013-1326-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-013-1326-8

Keywords

Search

Navigation