Mette S A, Pilewski J, Buck C A, Albelda S M
Department of Medicine, University of Pennsylvania, Philadelphia.
Am J Respir Cell Mol Biol. 1993 May;8(5):562-72. doi: 10.1165/ajrcmb/8.5.562.
The interactions of bronchial epithelial cells with the basement membrane control cell morphology, differentiation, and proliferation in addition to having a major role in malignant transformation. Since these interactions are mediated by the integrin family of cell adhesion receptors, we characterized the integrin repertoire and adhesive properties of normal human bronchial epithelial cells in culture and cell lines derived from nine lung carcinomas using subunit-specific monoclonal antibodies. In addition, the integrin repertoire of three of the transformed cell lines was reexamined after the cells formed tumor nodules in immunodeficient mice. Bronchial epithelial cells in culture expressed multiple integrin subunits with the capability of binding to collagen and laminin (alpha 2, alpha 3, and alpha 6) and at least two subunits that are capable of mediating adhesion to fibronectin (alpha 3 and an alpha v-containing integrin). The alpha v beta 3 vitronectin receptor was not present. This distribution closely mimicked that seen by bronchial epithelial cells in situ. Cell lines derived from transformed pulmonary epithelial cells showed great heterogeneity with respect to integrin expression--some showing fewer, some greater, and some the same types of integrins as nontransformed epithelial cells. Only slight changes in integrin expression were seen in tumor cells propagated in immunodeficient mice. Although the adhesion characteristics of the transformed cells mirrored their adhesion receptor profile, no correlation between integrin profile and the ability to grow in SCID mice was observed. This study defines the integrin repertoire of human bronchial epithelial cells and sets the stage for future investigations exploring how the regulation and signal transduction mechanisms of these receptors might affect important pulmonary processes such as bronchial cell differentiation, wound healing, and malignant transformation.
支气管上皮细胞与基底膜的相互作用不仅在恶性转化中起主要作用，还控制细胞形态、分化和增殖。由于这些相互作用是由细胞粘附受体的整合素家族介导的，我们使用亚基特异性单克隆抗体对培养的正常人支气管上皮细胞以及来自9种肺癌的细胞系的整合素组成和粘附特性进行了表征。此外，在三种转化细胞系在免疫缺陷小鼠中形成肿瘤结节后，重新检测了它们的整合素组成。培养的支气管上皮细胞表达多种整合素亚基，能够与胶原蛋白和层粘连蛋白结合（α2、α3和α6），以及至少两种能够介导与纤连蛋白粘附的亚基（α3和一种含αv的整合素）。不存在αvβ3玻连蛋白受体。这种分布与原位支气管上皮细胞所见的分布非常相似。源自转化肺上皮细胞的细胞系在整合素表达方面表现出很大的异质性——一些细胞系表达的整合素比未转化的上皮细胞少，一些更多，还有一些与未转化的上皮细胞相同类型。在免疫缺陷小鼠中传代的肿瘤细胞中，整合素表达仅出现轻微变化。尽管转化细胞的粘附特性反映了它们的粘附受体谱，但未观察到整合素谱与在SCID小鼠中生长能力之间的相关性。这项研究确定了人支气管上皮细胞的整合素组成，并为未来探索这些受体的调节和信号转导机制如何影响支气管细胞分化、伤口愈合和恶性转化等重要肺部过程的研究奠定了基础。
