Laminin receptor α6β4 integrin is highly expressed in ENU-induced glioma in rat

Laminins and their receptors influence neoplastic growth and invasive- hess. We recently reported the abnormal expression of a laminin receptor, α6β4 integrin, in human astrocytomas. To further investigate the role of α6β4 in gliomas, we produced an experimental model of glioma in rat by transplacental ethylnitrosourea (ENU) administration. This animal model allowed us to study the timing of α6β4 expression during tumor development and the topography of expression in the tumor and the surrounding tissue. Immunohistochemistry, in situ hybridization, and immunoprecipitation studies demonstrated that α6β4 heterodimer forms in experimental gliomas, and confirmed that α6β4 is expressed diffusely in neoplastic cells and reactive astrocytes, but not in normal glia surrounding the tumors. Interestingly, α6β4 was expressed from the early phases of tumor development, and more highly expressed by cells in the proliferative centers of the tumors. Both neoplastic cells and reactive astrocytes also expressed the glial growth factor (neuregulin) receptors, Erb-B2 and Erb-B3. Finally, α6β4 expression was reduced in a subset of tumor blood vessels. Thus, this study suggests a potential role for α6β4 in the pathogenesis of gliomas. Furthermore, this is the first description of altered integrin expression in experimental gliomas; transplacental ENU-induced gliomas in rat will provide a useful model to study the role of altered adhesion in the pathogenesis of human gliomas.