Christensen L
Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
APMIS Suppl. 1992;26:1-39.
Since Coman in 1944 observed that decreased adhesiveness is a characteristic of malignant cells and Grobstein 10 years later demonstrated that epithelial and mesenchymal cells influence each other when separated by a cell-impermeable filter, components of the extracellular matrix have been suspected of playing an active role in cancer growth. Breast cancer is frequently characterized by an increase in connective tissue fibroblastic cells and extracellular matrix, the nature and molecular composition of which is gradually being revealed. Two of the most studied and hence best known components of extracellular matrix are fibronectin and laminin. They are called adhesive or structural glycoproteins, because they are part of the stabilizing scaffold, which links connective tissue cells to each other (fibronectin) and connects connective tissues with parenchymatous cells via basement membranes (laminin). Both molecules harbour a variety of specific binding sites, which allow them to participate actively in basic dynamic processes such as cell modulation, -attachment, -spreading and -migration. Tetranectin is a recently discovered protein of human plasma and nucleated cells, which is suspected of participating in tissue degradation and proteolysis through its specific binding to plasminogen, a member of the plasminogen activation system. The immunohistochemical studies of fibronectin, laminin and tetranectin, on which this thesis is based, were undertaken in order to investigate if qualitative or quantitative changes of these proteins between benign and malignant breast tissue would reflect the net effect of the different inherent characteristics of breast cancer cells known from experimental studies (i.e. unanchored growth, proteolysis, metastatic spread and de novo production of extracellular matrix components). A significant increase in stromal fibronectin was a consistent finding in all infiltrating carcinomas, permitting the discrimination between such tumors and benign proliferative lesions as well as between carcinomas with a sarcomatoid appearance and true breast carcinomas. However, as a possible consequence of tumor heterogeneity this stromal reactivity pattern varied and tended to disappear focally along the invasive front of tumors with a high metastatic potential. A concurrent increase in the tumor cell expression of FN was found in poorly differentiated tumors, which could either be due to increased fibronectin production by the more anaplastic tumor cells or internalization of exogenous fibronectin bound to its receptor. Whereas most of the extracellular fibronectin in breast cancer is thought to be produced by the stromal fibroblasts, extracellular laminin is considered a product of the epithelial tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)
自1944年科曼观察到黏附性降低是恶性细胞的一个特征，以及10年后格罗布斯坦证明上皮细胞和间充质细胞在被细胞不可渗透的滤膜分隔时会相互影响以来，细胞外基质的成分一直被怀疑在癌症生长中发挥积极作用。乳腺癌的特征通常是结缔组织成纤维细胞和细胞外基质增加，其性质和分子组成正逐渐被揭示。细胞外基质中研究最多且因此最为人所知的两种成分是纤连蛋白和层粘连蛋白。它们被称为黏附性或结构性糖蛋白，因为它们是稳定支架的一部分，该支架将结缔组织细胞相互连接（纤连蛋白），并通过基底膜将结缔组织与实质细胞连接起来（层粘连蛋白）。这两种分子都有多种特异性结合位点，这使它们能够积极参与细胞调节、附着、铺展和迁移等基本动态过程。四连蛋白是一种最近在人血浆和有核细胞中发现的蛋白质，它被怀疑通过与纤溶酶原激活系统的成员纤溶酶原特异性结合而参与组织降解和蛋白水解。本论文所基于的对纤连蛋白、层粘连蛋白和四连蛋白的免疫组织化学研究，旨在调查这些蛋白质在良性和恶性乳腺组织之间的定性或定量变化是否会反映实验研究中已知的乳腺癌细胞不同固有特征的净效应（即无锚定生长、蛋白水解、转移扩散和细胞外基质成分的从头产生）。在所有浸润性癌中，基质纤连蛋白显著增加是一个一致的发现，这使得能够区分此类肿瘤与良性增生性病变，以及区分具有肉瘤样外观的癌和真正的乳腺癌。然而，作为肿瘤异质性的一个可能后果，这种基质反应模式各不相同，并且在具有高转移潜能的肿瘤的侵袭前沿局部趋于消失。在低分化肿瘤中发现肿瘤细胞FN表达同时增加，这可能是由于更间变的肿瘤细胞产生纤连蛋白增加，或者是与受体结合的外源性纤连蛋白内化所致。虽然乳腺癌中大多数细胞外纤连蛋白被认为是由基质成纤维细胞产生的，但细胞外层粘连蛋白被认为是上皮肿瘤细胞的产物。（摘要截选至400字）
