Skip to main content

Advertisement

Log in

CD44 expression and hyaluronic acid binding of malignant glioma cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigated expression of the hyaluronic acid receptor CD44 protein in five human (T98G, A172, U87MG, 86HG39, 85HG66) and two rat (C6, 9L) glioma cell lines. Influence of anti-CD44 antibody and hyaluronidase-preincubation on the HA-binding was determined using HA/BSA (bovine serum albumin)-coated culture plates. While all gliomas were highly positive for CD44 with no differences in the number of positive staining cells, median fluorescence intensity decreased as follows: C6>T98G>9L>85HG66> 86HG39>A172> U87MG. Using HA/BSA coated culture plates the relative levels of specific adhesion to HA were determined as T98G>A172>9L>86HG39>U87MG> 85HG66. C6 cells failed to bind HA specifically. Incubation with anti-human-CD44 MAb significantly decreased HA-adhesion of T98G, A172, 85HG66 and U87MG human glioma cells. However the binding capacity was completely blocked only in 85HG66 cells. The three other cell lines kept a specific HA-adhesion after saturation of the receptor. Hyaluronidase pretreatment markedly enhanced HA-adhesion of C6 and 9L rat glioma cells. These results suggest that (i) HA-adhesion of malignant glioma cells is mainly, but not only, mediated by CD44, (ii) expression of CD44 does not correspond with adhesion capacity and (iii) cell-bound glycosaminoglycans may influence glioma cell adhesion to extracellular HA.

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.

Similar content being viewed by others

References

  1. Kim TS, Halliday AL, Hedley-Whyte ET, Convery K. Correlates of survival and Daumas-Duport grading system for astrocytomas. J Neurosurg 1991; 74: 27–37.

    Google Scholar 

  2. Pilkington GJ. Tumour cell migration in the central nervous system. Brain Pathol 1994; 4: 157–66.

    Google Scholar 

  3. Rutka JT, Apodaca G, Stern R, Rosenblum M. The extracellular matrix of the central and peripheral nervous systems: structure and function. J Neurosurg 1988; 69: 155–70.

    Google Scholar 

  4. Venstrom KA, Reichard LF. Extracellular matrix 2: role of extracellular matrix molecules and their receptors in the nervous system. FASEB J 1993; 7: 996–1003.

    Google Scholar 

  5. Bignami A, Hosley M, Dahl D. Hyaluronic acid and hyaluronic acidbinding proteins in brain extracellular matrix. Anat Embryol 1993; 188: 419–33.

    Google Scholar 

  6. Bignami A, Asher R. Some observations on the localization of hyaluronic acid in adult, newborn and embryonal rat brain. Int J Devl Neurosci 1992; 10: 45–57.

    Google Scholar 

  7. De Clerck YA, Shimada H, Gonzales-Gomez I, Raffel C. Tumoral invasion in the central nervous system. J Neurooncol 1994; 18: 111–21.

    Google Scholar 

  8. Merzak A, Koocheckpour S, Pilkington GJ. CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res 1994; 54: 3988–92.

    Google Scholar 

  9. Radotra B, McCormick D. Glioma invasion in vitro is mediated by CD44–Hyaluronan interactions. J Pathol 1997; 181: 434–8.

    Google Scholar 

  10. Pilkington GJ. The role of extracellular matrix in neoplastic glial invasion of the nervous system. Braz J Med Biol Res 1996; 29: 1159–72.

    Google Scholar 

  11. Knüpfer MM, Poppenborg H, Hotfilder M et al. Hyaluronic acid binding capacity of malignant glioma cells. Anticancer Res 1998; 18: 353–6.

    Google Scholar 

  12. Tung JS, Mark GE, Hollis GF. A microplate assay for hyaluronidase and hyaluronidase inhibitors. Anal Biochem 1994; 223: 149–52.

    Google Scholar 

  13. Hansen M, Nielsen SE, Berg K. Re-examination and further development of a precise and rapid dye method for measure cell growth/cell kill. J Immunol Methods 1991; 119: 203–10.

    Google Scholar 

  14. Asher R, Bignami A. Hyaluronate binding and CD44 expression in human glioblastoma cells and astrocytes. Exp Cell Res 1992; 203: 80–90.

    Google Scholar 

  15. Sakai H, Nalashima S, Shin-ichi Y et al. Suppressed expression of CD44 variant isoforms during human glioma A172 cell differentiation by cyclic AMP. Neurosci Lett 1996; 210: 189–92.

    Google Scholar 

  16. Li H, Hamou MF, de-Tribolet N, Jaufeerally R et al. Variant CD44 adhesion molecules are expressed in human brainmetastases but not in glioblastomas. Cancer Res 1993; 53: 5345–9.

    Google Scholar 

  17. Eibl RH, Pietsch T, Moll J et al. Expression of variant CD44 epitopes in human astrocytic brain tumors. J Neurooncol 1995; 26: 165–70.

    Google Scholar 

  18. Kaaijk P, Troost D, Morsink F et al. Expression of CD44 splice variants in human primary brain tumors. J Neurooncol 1995; 26: 185–90.

    Google Scholar 

  19. Aruffo A, Stamenkovic I, Melnick M et al. CD44 is the principal cell surface receptor for hyaluronate. Cell 1990; 61: 1303–13.

    Google Scholar 

  20. Lesley J, Hyman R. CD44 structure and function. Front Biosci 1998; 3: D616–D330.

    Google Scholar 

  21. Frank S, Rihs HP, Stocker W et al. Combined detection of CD44 isoforms by exon-specific RT-PCR and immunohistochemistry in primary human brain tumors and brain metastasis. Biochem Biophys Res Commun 1996; 222: 794–801.

    Google Scholar 

  22. Catterall JB, Gardner MJ, Jones LM, Turner GA. Binding of ovarian cancer cells to immmobilized hyaluronic acid. Glycoconj J 1997; 14:647–9.

    Google Scholar 

  23. Lesley J, Hyman R, English N et al. CD44 in inflammation and metastasis. Glycoconj J 1997; 14:611–22.

    Google Scholar 

  24. Skelton TP, Zeng C, Nocks A et al. Glycosylation provides both stimulatory and inhibitory effects on cell surface and soluble CD44 binding hyaluronan. J Cell Biol 1998; 140: 431–46.

    Google Scholar 

  25. Zheng Z, Cummings R, Pummill P, Kincade P. Growth as a solid tumor or reduced glucose concentrations in culture reversible induce CD44–mediated hyaluronan recognition by Chinese hamster ovary cells. J Clin Invest 1997; 100: 1217–29.

    Google Scholar 

  26. Yu Q, Toole BP, Stamenkovic I. Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function. J Exp Med 1997; 186: 1985–96.

    Google Scholar 

  27. Lokeshwar VB, Fregien N, Bourguignon LYW. Ankyrin-binding Domain of CD44 (GP85) is required for the expression of hyaluronic acid-mediated adhesion function. J Cell Biol 1994; 126: 1099–109.

    Google Scholar 

  28. Zheng Z, Katoh S, Qi H et al. Monoclonal antibodies and their influence on hyaluronan recognition. J Cell Biol 1995; 130: 485–95.

    Google Scholar 

  29. Delpech B, Maingonnat C, Girard N. Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma. Eur J Cancer 1993; 29: 1012–17.

    Google Scholar 

  30. Hall CL, Turley EA. Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. J Neurooncol 1995; 26: 221–9.

    Google Scholar 

  31. Baumgartner G, Horaczek A, Grunert P et al. Hyaluronidase als Zusatz zur zytostatischen Chemotherapie bei Glioblastomen. Onkologie 1987; 10: 100–3

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knüpfer, M., Poppenborg, H., Hotfilder, M. et al. CD44 expression and hyaluronic acid binding of malignant glioma cells. Clin Exp Metastasis 17, 81–86 (1999). https://doi.org/10.1023/A:1026425519497

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026425519497

Navigation