Behavior of the basement membrane during carcinoma cell invasion in chemically induced carcinomas of the skin.

Abstract

Immunohistochemical localizations of the intrinsic basal lamina (BL) components laminin-1 and type IV collagen, the adhesion molecules type VII collagen and laminin receptor (alpha 6 beta 1 integrin), and the type IV collagenase (72 kDa, MMP2) were analyzed in carcinomas of the mouse skin which were chemically induced by benzo[a]pyrene with or without the addition of the promotor phorbol 12-myristate 13-acetate. Normal skin, dysplastic lesions, and invasive carcinomas were investigated by histological and immunohistochemical (immunofluorescence and APAAP) methods. A regular and continuous staining of laminin-1 and type IV collagen was present in the normal skin and in areas of slight and moderate dysplasia. Underneath highly dysplastic epithelium, the BL became thin, loosened and sometimes disrupted, and accumulations of globular BL material were found in the connective tissue underneath the BL. Type VII collagen retained a more linear, continuous and uniform distribution in the areas of progressed epithelial dysplasia. All invasive carcinomas were characterized by a BL which was disrupted by gaps of varying size but, again, showed a more uniform and less discontinuous distribution of the anchoring molecule type VII collagen. Expression of the integrin laminin receptor investigated increased quantitatively in dysplastic lesions and in areas of invasive carcinomas, showing a circular presence at the surface of most epithelial cells of the basal and spinous layers of the epidermis, whereas, in the normal skin, the laminin receptor was polarized to the basal and lateral cell membrane of basal epithelial cells in contact with the BL. These results suggest that the discontinuities occurring in the BL during carcinoma cell invasion are not caused by a local loss of the anchoring molecules type VII collagen and/or laminin receptor, though alterations in the pattern of expression of the laminin receptor document fundamental changes in the cellular organization occurring during malignant transformation. On the other hand, the presence of the type IV collagenase increased in epithelial dysplasias and invasive carcinomas. In many dysplastic lesions, it was deposited in a plaque-like and sometimes linear manner near the basement membrane (BM) region indicating that, in chemically induced carcinomas, this enzyme may be involved in the process of BM perforation during carcinoma cell invasion.