Tenascin and Extracellular Matrix: Possible Biological Implications During Regression and Carcinogenesis of the Prostate

Abstract

The role of extracellular matrices (ECM) in normal prostate function during the regression of the prostate and in carcinogenesis of this organ has only recently attracted the attention of various research groups. Histologically, the most prominent structure of the ECM in the prostate is the basement membrane (BM). This structure deserves particular attention, since it exhibits unique features in the prostate, not observable in other organs. In the fetal and adult prostate and in various hyperplastic conditions the BM was found to be continuous with local thickenings and therefore rather inconspicious compared to the BM of other organs (Bonkhoff et al. 1991). However, whereas adenocarcinoma cells of most other organs degrade and invade the BM after having acquired their invasive phenotype, prostatic tumor cells, independent of their degree of differentiation, persist with their pronounced BM (Bonkhoff et al. 1991, 1992). Even highly malignant anaplastic and small cell carcinomas, irradiated and/or hormonally treated tumors, as well as lymphatic or hematogenous mestastases showed distinct BM formations in contact with the stroma (Bonkhoff et al. 1992). These observations suggest a close association and a strong dependency of the normal and carcinogenic prostatic epithelium for BM anchoring. Experimental evidence in favor of this assumption has been delineated from in vitro findings in cultured primary human prostatic epithelial cells. For these cells it has been demonstrated that a reconstituted BM (Matrigel) promotes morphological and functional differentiation in vitro (Fong et al. 1991). In vitro experiments further suggested that this reconstituted BM is able to stimulate the growth of human prostatic carcinoma in athymic mice and to control the migration of these tumor cells in cell culture (Passaniti et al. 1992). In this context it is important to mention that highly metastatic prostate tumor cells could be selected out of a wild-type tumor cell line using a Matrigel invasion assay. Analysis of the cell surface integrins showed that the metastatic phenotype exhibited down-regulation of the α₃β₁ integrin and an overexpression of the α₆β₄ integrin. Further, whereas the α₆-subunit was complexed to β₁ subunit in wild-type cells (Dedhar et al. 1993), it was predominantly associated with β₄ in the metastatic cells. Alterations in the expression of the α₃β₁ and α₆β₄ integrins may thus allow these cells to become more invasive and lead to an increased propensity for metastasis.