Laminin receptor alpha 6 beta 4 integrin is highly expressed in ENU-induced glioma in rat

Laminins and their receptors influence neoplastic growth and invasiveness. We recently reported the abnormal expression of a laminin receptor, alpha 6 beta 4 integrin, in human astrocytomas. To further investigate the role of alpha 6 beta 4 in gliomas, we produced an experimental model of glioma in rat by transplacental ethylnitrosourea (ENU) administration. This animal mo del allowed us to study the timing of alpha 6 beta 4 expression during tumo r development and the topography of expression in the tumor and the surroun ding tissue. Immunohistochemistry, in situ hybridization, and immunoprecipi tation studies demonstrated that alpha 6 beta 4 heterodimer forms in experi mental gliomas, and confirmed that alpha 6 beta 4 is expressed diffusely in neoplastic cells and reactive astrocytes, but not in normal glia surroundi ng the tumors. Interestingly, alpha 6 beta 4 was expressed from the early p hases of tumor development, and more highly expressed by cells in the proli ferative centers of the tumors. Both neoplastic cells and reactive astrocyt es also expressed the glial growth factor (neuregulin) receptors, Erb-B2 an d Erb-B3. Finally, alpha 6 beta 4 expression was reduced in a subset of tum or blood vessels. Thus, this study suggests a potential role for alpha 6 be ta 4 in the pathogenesis of gliomas. Furthermore, this is the first descrip tion of altered integrin expression in experimental gliomas; transplacental ENU-induced gliomas in rat will provide a useful model to study the role o f altered adhesion in the pathogenesis of human gliomas. GLIA 26:55-63, 199 9. (C) 1999 Wiley-Liss, Inc.