Mechtersheimer G, Barth T, Quentmeier A, Möller P
Institute of Pathology, University of Heidelberg, Federal Republic of Germany.
Lab Invest. 1994 May;70(5):740-52.
Extracellular matrix proteins and their receptors take part in physiologic neural development and organization and also in abnormal neoplastic growth and spread. There is increasing evidence for the implication of integrins in these processes.
Human 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 immunostained using an indirect streptavidin/biotin-peroxidase method and monoclonal antibodies against beta 1, alpha 1 to alpha 6, beta 3, alpha v, and beta 4 subunits.
Both small- and large-diameter nerve fibers of normal peripheral nerve trunks were consistently beta 1+, alpha 6+, and beta 4+ in the absence of alpha 3, alpha 4, alpha 5, and beta 3. Small-diameter nerve fibers further expressed alpha 1, alpha 2, and alpha v. Meissner's corpuscles and inner cores of Pacinian corpuscles shared the integrin repertoire of small-diameter nerve fibers with additional expression of alpha 3; outer cores of Pacinian corpuscles were beta 1+, alpha 3+, alpha 6+, and beta 4+. Regenerating nerve fibers paralleled the integrin profile of normal peripheral nerves. By contrast, malignant schwannomas showed considerable changes in integrin expression. These alterations consisted mainly in a neoexpression of alpha 3, alpha 4, and alpha 5 and in an abnormal loss of alpha 6 and beta 4. Expression of alpha 1, alpha 2, and alpha v was variable; absence of beta 3 was generally conserved. In ganglion cells, integrin expression was restricted to beta 1 and alpha 3 subunits, and chromaffine cells of the adrenal medulla even lacked any detectable beta 1, beta 3, and beta 4 integrin subunits. (Ganglio)-neuroblastomas, however, were beta 1+, alpha 1+, and alpha 3+, whereas primitive peripheral neuroectodermal tumors were beta 1+ and alpha 5+.
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 changes in this integrin profile. The observation of neoplasia-associated abnormalities underlines the important role of integrins in the orderly development and maintenance of human neural tissue. Some aspects of the emerging integrin subunit patterns are useful for the differential diagnosis of neural soft-tissue tumors.
细胞外基质蛋白及其受体参与生理性神经发育和组织构建，也与肿瘤的异常生长和扩散有关。越来越多的证据表明整合素参与了这些过程。
检测了含有外周和自主神经系统非肿瘤性神经细胞的人体组织以及一系列全面的神经肿瘤中β1、β3和β4整合素的原位表达。每个组织样本的连续冰冻切片采用间接链霉亲和素/生物素-过氧化物酶法和针对β1、α1至α6、β3、αv和β4亚基的单克隆抗体进行免疫染色。
正常周围神经干的小直径和大直径神经纤维始终呈β1+、α6+和β4+，不存在α3、α4、α5和β3。小直径神经纤维还表达α1、α2和αv。迈斯纳小体和环层小体的内核具有与小直径神经纤维相同的整合素表达谱，并额外表达α3；环层小体的外核呈β1+、α3+、α6+和β4+。再生神经纤维的整合素表达谱与正常周围神经相似。相比之下，恶性神经鞘瘤的整合素表达有显著变化。这些改变主要包括α3、α4和α5的新表达以及α6和β4的异常缺失。α1、α2和αv的表达可变；β3的缺失通常保持不变。神经节细胞的整合素表达仅限于β1和α3亚基，肾上腺髓质的嗜铬细胞甚至缺乏任何可检测到的β1、β3和β4整合素亚基。然而，（神经节）神经母细胞瘤呈β1+、α1+和α3+，而原始外周神经外胚层肿瘤呈β1+和α5+。
非肿瘤性人类神经细胞表现出β1、β3和β4整合素亚基表达的复杂且同时具有差异的模式。恶性转化导致这种整合素表达谱发生显著变化。对肿瘤相关异常的观察强调了整合素在人类神经组织有序发育和维持中的重要作用。新出现的整合素亚基模式的某些方面有助于神经软组织肿瘤的鉴别诊断。
