Ingber D E, Madri J A, Jamieson J D
Am J Pathol. 1985 Nov;121(2):248-60.
The authors have analyzed the structural relations of a nonmetastatic rat pancreatic acinar carcinoma and contrasted them with those of normal exocrine pancreas in order to better define the role of basement membrane (BM) in early stages of neoplastic disorganization. These studies showed that normal acinar cells rested on continuous BM (containing laminin, heparan sulfate proteoglycan, and Type IV and V collagens) and displayed a polarized distribution of intracellular organelles, cytoskeletal assemblies (concentration of actin within terminal web), and distinct membrane domains (apical leucine aminopeptidase). In contrast, the parenchyma of the pancreatic acinar carcinoma was free of all BM components except for a discontinuous array of laminin. In these regions, acinar tumor cells appeared randomly oriented, displayed actin in uniform cortical distributions, and lost membrane polarity. However, when tumor cells contacted mesenchymally derived connective tissue along tumor capsule and vascular adventitia, they accumulated intact BM and reoriented in a manner reminiscent of normal pancreas. Tumor cell reorganization was observed in the absence of formation of full junctional complexes or normally polarized membrane domains, although leucine aminopeptidase appeared to be excluded from regions of tumor cell surfaces that were in direct contact with BM. The loss of normal epithelial cell-cell arrangements that is the hallmark of early stages of tumor formation could therefore result from failure to match increases in cell number with commensurate BM extension.
作者分析了一种非转移性大鼠胰腺腺泡癌的结构关系，并将其与正常外分泌胰腺的结构关系进行对比，以便更好地确定基底膜（BM）在肿瘤性结构紊乱早期阶段的作用。这些研究表明，正常腺泡细胞位于连续的基底膜上（含有层粘连蛋白、硫酸乙酰肝素蛋白聚糖以及IV型和V型胶原），并表现出细胞内细胞器、细胞骨架组件（肌动蛋白在终末网内集中）以及不同膜结构域（顶端亮氨酸氨肽酶）的极化分布。相比之下，胰腺腺泡癌的实质除了有不连续的层粘连蛋白排列外，没有所有基底膜成分。在这些区域，腺泡肿瘤细胞呈现随机取向，肌动蛋白呈均匀的皮质分布，并且失去了膜极性。然而，当肿瘤细胞沿着肿瘤包膜和血管外膜接触间充质来源的结缔组织时，它们会积累完整的基底膜，并以类似于正常胰腺的方式重新定向。在没有形成完整连接复合体或正常极化膜结构域的情况下观察到肿瘤细胞重排，尽管亮氨酸氨肽酶似乎被排除在与基底膜直接接触的肿瘤细胞表面区域之外。因此，肿瘤形成早期阶段的标志性特征——正常上皮细胞间排列的丧失，可能是由于细胞数量增加与相应基底膜扩展不匹配所致。
