Invasive behaviour of human gliomas is mediated by interindividually different integrin patterns.

BACKGROUND

Glioma invasion is still a major obstacle for successful therapy. In the past we could demonstrate that glioma invasion is mediated by different adhesion molecules of the integrin family. Here we investigated whether a common pattern of integrin profiles might be involved, potentially providing a therapeutical avenue.

MATERIAL AND METHODS

Multicellular spheroids were generated out of three human cell lines (GaMG, U373, U251) and from tumor biopsies of 9 human glioblastomas. After confrontation with rat brain aggregates, functional blocking antibodies against different integrin subunits (alpha 2, alpha 3, alpha v, alpha 1, alpha v beta 3, alpha v beta 5) or four different disintegrines (kistrin, echistatin, eristostatin, flavoridin) were added. Integrin patterns of the human cell lines/specimens were determined by FACScan or immunohistochemistry.

RESULTS

In cell lines, antibodies against alpha 2, alpha 3, alpha v and alpha v beta 5 effectively reduced invasion into rat brain aggregates. Little effect could be observed with the anti-beta 1- or with anti-alpha v beta 3- antibodies. In primary tumor specimens, however, a different invasion pattern in regard to its integrin dependency emerged with antibodies against the alpha 3-chain or the alpha v beta 3 integrin being the most effective. Invasion of primary tumor tissue into the brain aggregates was by far more aggressive compared to that of the cell lines. Accordingly, it was less influenced by integrin antibodies. The disintegrines affected migration of glioma cells on purified ECM substrates in a heterogeneous matter, but had no impact on tumor invasion into brain aggregates.

CONCLUSION

Although invasion of human gliomas is mediated by integrins, due to the heterogeneity of its dependency on different integrins this approach seems not to be appropriate to sufficiently alter glioma invasion in a therapeutical neuro-oncological setting.