DIFFERENTIAL EXPRESSION OF BETA-1, BETA-3, AND BETA-4 INTEGRIN SUBUNITS IN NONNEOPLASTIC NEURAL CELLS OF THE PERIPHERAL AND AUTONOMIC NERVOUS-SYSTEM AND IN TUMORS DERIVED FROM THESE CELLS

BACKGROUND: Extracellular matrix proteins and their receptors take par t in physiologic neural development and organization and also in abnor mal neoplastic growth and spread. There is increasing evidence for the implication of integrins in these processes. EXPERIMENTAL DESIGN: Hum an tissues containing nonneoplastic neural cells of the peripheral and autonomic nervous system and a comprehensive series of neural tumors were examined for the in situ expression of beta 1, beta 3, and beta 4 integrins. Serial frozen sections of each tissue sample were immunost ained using an indirect streptavidin/biotin-peroxidase method and mono clonal antibodies against beta 1, alpha 1 to alpha 6, beta 3, alpha v, and beta 4 subunits. RESULTS: Both small- and large-diameter nerve fi bers of normal peripheral nerve trunks were consistently beta 1(+), al pha 6(+) and beta 4(+) in the absence of alpha 3, alpha 4, alpha 5, an d beta 3. Small-diameter nerve fibers further expressed alpha 1, alpha 2, and alpha v. Meissner's corpuscles and inner cores of Pacinian cor puscles shared the integrin repertoire of small-diameter nerve fibers with additional expression of alpha 3; outer cores of Pacinian corpusc les were beta 1(+), alpha 3(+), alpha 6(+), and beta 4(+). Regeneratin g nerve fibers paralleled the integrin profile of normal peripheral ne rves. By contrast, malignant schwannomas showed considerable changes i n integrin expression. These alterations consisted mainly in a neoexpr ession of alpha 3, alpha 4, and alpha 5 and in an abnormal loss of alp ha 6 and beta 4. Expression of alpha 1, alpha 2, and alpha v was varia ble; absence of beta 3 was generally conserved. In ganglion cells, int egrin expression was restricted to beta 1 and alpha 3 subunits, and ch romaffine cells of the adrenal medulla even lacked any detectable beta 1, beta 3, and beta 4 integrin subunits. (Ganglio-)neuroblastomas, ho wever, were beta 1(+), alpha 1(+), and alpha 3(+), whereas primitive p eripheral neuroectodermal tumors were beta 1(+) and alpha 5(+). CONCLU SIONS: Nonneoplastic human neural cells exhibit a complex and, at the same time, differential pattern of beta 1, beta 3, and beta 4 integrin subunit expression. Malignant transformation leads to considerable ch anges in this integrin profile. The observation of neoplasia-associate d abnormalities underlines the important role of integrins in the orde rly development and maintenance of human neural tissue. Some aspects o f the emerging integrin subunit patterns are useful for the differenti al diagnosis of neural soft-tissue tumors.