Role of basal lamina in neoplastic disorganization of tissue architecture.

Abstract

We have studied a transplantable carcinoma of the rat pancreas [Reddy, J. K. & Rao, M. S. (1977( Science 198, 78-80] that is composed of cytologically differentiated acinar cells that have lost their epithelial orientation and do not form acini. Light microscopy shows, however, consistent palisading, reorientation, and polarization of these cells in areas of contact with the vasculature. Electron microscopy reveals a normal basal lamina (BL) along the basal portions of repolarized tumor cells that is physically separate from the endothelial BL. We used indirect immunofluorescence to examine the distribution of BL constituents, laminin (Lm) and type IV collagen (type IV), within the different microenvironments of this tumor. In normal pancreas, Lm and type IV are distributed linearly, outlining acini and blood vessels. In the tumor parenchyma, type IV is not detected, whereas Lm appears in a punctate distribution outlining cells. Reorientation of tumor cells is observed only along linearly deposited Lm and type IV bordering vessels. These data indicate that this nonmetastatic tumor has lost the ability to produce or maintain a complete BL within its disorganized parenchyma, while its cells retain the capacity to produce and reorganize along liner BL when in contact with vascular adventitia. We suggest that failure to maintain a complete BL may be involved in the neoplastic disorganization of normal tissue architecture as well as in the breakdown of boundaries during the development of invasive carcinomata.