Skip to main content

Advertisement

Log in

Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Podoplanin (aggrus) is a mucin-like transmembrane sialoglycoprotein that is expressed on lymphatic endothelial cells. Podoplanin is putatively involved in cancer cell migration, invasion, metastasis, and malignant progression and may be involved in platelet aggregation. Previously, we showed upregulated expression of podoplanin in central nervous system (CNS) germinomas, but not in non-germinomatous germ cell tumors, except for parts of immature teratomas in limited numbers. However, little information exists about its role in CNS astrocytic tumors. In this study, 188 astrocytic tumors (30 diffuse astrocytomas, 43 anaplastic astrocytomas, and 115 glioblastomas) were investigated using immunohistochemistry with an anti-podoplanin antibody, YM-1. In 11 of 43 anaplastic astrocytomas (25.6%) and in 54 of 115 glioblastomas (47.0%), podoplanin was expressed on the surface of anaplastic astrocytoma cells and glioblastoma cells, especially around necrotic areas and proliferating endothelial cells. However, the surrounding brain parenchyma was not stained by YM-1. On the other hand, podoplanin expression was not observed in diffuse astrocytoma (0/30: 0%). Furthermore, we investigated the expression of podoplanin using quantitative real-time PCR and Western blot analysis in 54 frozen astrocytic tumors (6 diffuse astrocytomas, 14 anaplastic astrocytomas, and 34 glioblastomas). Podoplanin mRNA and protein expression were markedly higher in glioblastomas than in anaplastic astrocytomas. These data suggest that podoplanin expression might be associated with malignancy of astrocytic tumors.

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

Similar content being viewed by others

References

  1. Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G, Kriehuber E, Diem K, Weninger W, Tschachler E, Alitalo K, Kerjaschki D (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394

    PubMed  CAS  Google Scholar 

  2. DeAngelis LM (2001) Brain tumors. N Engl J Med 344:114–123

    Article  PubMed  CAS  Google Scholar 

  3. Geiger KD, Stoldt P, Schlote W, Derouiche A (2000) Ezrin immunoreactivity is associated with increasing malignancy of astrocytic tumors but is absent in oligodendrogliomas. Am J Pathol 157:1785–1793

    PubMed  CAS  Google Scholar 

  4. Giese A, Bjerkvig R, Berens ME, Westphal M (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21:1624–1636

    Article  PubMed  CAS  Google Scholar 

  5. Honn KV, Tang DG, Crissman JD (1992) Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev 11:325–351

    Article  PubMed  CAS  Google Scholar 

  6. Kaneko M, Kato Y, Kunita A, Fujita N, Tsuruo T, Osawa M (2004) Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/podoplanin) molecules expressed in Chinese Hamster Ovary cells. J Biol Chem 279:38838–38843

    Article  PubMed  CAS  Google Scholar 

  7. Kato Y, Fujita N, Kunita A, Sato S, Kaneko M, Osawa M, Tsuruo T (2003) Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. J Biol Chem 278:51599–51605

    Article  PubMed  CAS  Google Scholar 

  8. Kato Y, Sasagawa I, Kaneko M, Osawa M, Fujita N, Tsuruo T (2004) Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors. Oncogene 23:8552–8556

    Article  PubMed  CAS  Google Scholar 

  9. Kato Y, Kaneko M, Sata M, Fujita N, Tsuruo T, Osawa M (2005) Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma. Tumor Biol 26:195–200

    Article  CAS  Google Scholar 

  10. Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncology 1:44–51

    Article  PubMed  CAS  Google Scholar 

  11. Kleihues P, Burger PC, Collins VP, Newcomb EW, Ohgaki H, Cavenee WK (2000) Astrocytic tumors. Glioblastoma. In: Kleihues P, Cavenee WK (eds) Pathology and genetics of tumours of the nervous system. International Agency for Research on Cancer Press, Lyons, France, pp 29–39

    Google Scholar 

  12. Martin-Villar E, Scholl FG, Gamallo C, Yurrita MM, Munoz-Guerra M, Cruces J, Quintanilla M (2005) Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. Int J Cancer 113:899–910

    Article  PubMed  CAS  Google Scholar 

  13. Mishima K, Kato Y, Kaneko KM, Nakazawa Y, Kunita A, Fujita N, Tsuruo T, Nishikawa R, Hirose T, Matsutani M (2006) Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma. Acta Neuropathol (Berl) (in press)

  14. Ordonez NG (2005) D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol 36:372–380

    Article  PubMed  CAS  Google Scholar 

  15. Roy S, Chu A, Trojanowski JQ, Zhang PJ (2005) D2-40, a novel monoclonal antibody against the M2A antigen as a marker to distinguish hemangioblastomas from renal cell carcinomas. Acta Neuropathol (Berl) 109:497–502

    Article  CAS  Google Scholar 

  16. Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, Williams M, Dvorak AM, Dvorak HF, Oliver G, Detmar M (2003) T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J 22:3546–3556

    Article  PubMed  CAS  Google Scholar 

  17. Schacht V, Dadras SS, Johnson LA, Jackson DG, Hong YK, Detmar M (2005) Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. Am J Pathol 166:913–921

    PubMed  CAS  Google Scholar 

  18. Scholl FG, Gamallo C, Vilaro S, Quintanilla M (1999) Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci 112:4601–4613

    PubMed  CAS  Google Scholar 

  19. Scholl FG, Gamallo C, Quintanilla M (2000) Ectopic expression of PA2.26 antigen in epidermal keratinocytes leads to destabilization of adherens junctions and malignant progression. Lab Invest 80:1749–1759

    Article  PubMed  CAS  Google Scholar 

  20. Shibahara J, Kashima T, Kikuchi Y, Kunita A, Fukayama M (2006) Podoplanin is expressed in subsets of tumors of the central nervous system. Virchows Arch (in press)

  21. Sugimoto Y, Watanabe M, Oh-hara T, Sato S, Isoe T, Tsuruo T (1991) Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation. Cancer Res 51:921–925

    PubMed  CAS  Google Scholar 

  22. Tsuruo T, Yamori T, Naganuma K, Tsukagoshi S, Sakurai Y (1983) Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26. Cancer Res 43:5437–5442

    PubMed  CAS  Google Scholar 

  23. Tynninen O, Carpen O, Jaaskelainen J, Paavonen T, Paetau A (2004) Ezrin expression in tissue microarray of primary and recurrent gliomas. Neuropathol Appl Neurobiol 30:472–477

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Kanae Foundation for Life and Socio-medical Science (to Y.K.) and by Osaka Cancer Research Foundation (to Y.K.). We thank Drs Fujita and Tsuruo (University of Tokyo) for their great help, and Ms Kunita, Mr Nakazawa (University of Tokyo), Ms Totake, and Ms Kobo (Saitama Medical School) for their kind assistance. We thank Dr Sugiyama (Hiroshima University) for providing us clinical samples.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yukinari Kato.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mishima, K., Kato, Y., Kaneko, M.K. et al. Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. Acta Neuropathol 111, 483–488 (2006). https://doi.org/10.1007/s00401-006-0063-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-006-0063-y

Keywords

Navigation