Neoplastic disorganization of pancreatic epithelial cell-cell relations. Role of basement membrane.

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.