Koukoulis G K, Virtanen I, Korhonen M, Laitinen L, Quaranta V, Gould V E
Department of Pathology, Rush Medical College, Chicago, Illinois 60612.
Am J Pathol. 1991 Oct;139(4):787-99.
Integrins comprise a family of transmembrane glycoproteins that modulate cell-matrix and cell-cell relationships by acting as receptors to extracellular protein ligands, and also as direct adhesion molecules. The authors studied by immunohistochemistry the distribution of the alpha 1-6,v and the beta 1,3,4 subunits of integrins in samples of normal breast, the spectrum of fibrocystic disease (FCD), and representative benign and malignant neoplasms. Monoclonal antibodies (Mabs) specific for each subunit were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence microscopy with the Mabs and a polyclonal antiserum to myosin. The authors found that the alpha 1-3,6,v and the beta 1, integrin subunits were detectable in the normal breast parenchyma; myoepithelial cells were consistently more prominently stained than the basolateral aspect of the luminal cells. This immunoprofile was retained, and in cases enhanced through the spectrum of FCD, in benign tumors and in ductal and lobular carcinomas in situ. In most infiltrating ductal carcinomas, integrin staining tended to decrease except for some cases that reacted strongly for the alpha v subunit. Several mucinous carcinomas reacted strongly for alpha 2,3,6,v and beta 4 subunits, and even more so for the alpha 5 subunit that was not found in the normal breast. Subsets of infiltrating lobular carcinomas stained convincingly for alpha 1,3,6,v and beta 1 subunits in delicate but abundant kinetopodia. Our findings indicate that in hyperplasias and in benign tumors integrin expression patterns parallel those of the normal breast, whereas in carcinomas, variations include decrease, enhancement, and emergence of certain subunits that are not in the normal repertory. Alterations of integrin expression parallel phenotypic changes in breast carcinoma cells; they also reflect their disrupted interaction with the similarly disrupted extracellular matrix. Enhancement of certain integrins in some carcinomas may reflect the selection of subpopulations with increased binding capacity which in turn may impact on their invasive and metastatic properties.
整合素是一族跨膜糖蛋白，它们作为细胞外蛋白配体的受体，同时也作为直接黏附分子，调节细胞与基质以及细胞与细胞之间的关系。作者采用免疫组织化学方法研究了整合素α1 - 6、v以及β1、3、4亚基在正常乳腺样本、纤维囊性疾病（FCD）谱系以及典型良性和恶性肿瘤中的分布情况。针对每个亚基的单克隆抗体（Mab）通过抗生物素蛋白 - 生物素复合物法应用于冰冻切片；部分选定样本通过与Mab和抗肌球蛋白多克隆抗血清进行双重免疫荧光显微镜检查。作者发现，在正常乳腺实质中可检测到α1 - 3、6、v以及β1整合素亚基；肌上皮细胞的染色始终比管腔细胞的基底外侧更明显。这种免疫表型在FCD谱系、良性肿瘤以及原位导管癌和小叶癌中得以保留，且在某些情况下有所增强。在大多数浸润性导管癌中，整合素染色趋于减少，但有一些病例对αv亚基反应强烈。一些黏液癌对α2、3、6、v和β4亚基反应强烈，对正常乳腺中未发现的α5亚基反应更强。浸润性小叶癌的某些亚群在纤细但丰富的动纤毛中，α1、3、6、v和β1亚基染色明显。我们的研究结果表明，在增生和良性肿瘤中，整合素表达模式与正常乳腺相似，而在癌中，变化包括某些亚基的减少、增强以及正常表达谱中未出现的亚基的出现。整合素表达的改变与乳腺癌细胞的表型变化平行；它们还反映了细胞与同样受到破坏的细胞外基质之间相互作用的紊乱。某些癌中特定整合素的增强可能反映了具有增强结合能力的亚群的选择，这反过来可能影响它们的侵袭和转移特性。
