Epithelial-stromal interactions in colon cancer.

In this paper investigations concerning the interactions at the interface between tumor cells and tumor stroma are reviewed. As a model for tumor cell-extracellular matrix interaction human colorectal carcinoma cell lines, in vitro and in vivo, in nude mouse xenografts, were chosen. Based on the available data and on a review of the literature the following conclusions can be drawn. Most malignant epithelial neoplasms at the site of tumor cell invasion display defects in the epithelial basement membrane. This is not merely the result of enzymatic dissolution but rather reflects a shift in basement membrane turnover towards degradation. Elsewhere in the same primary tumor or in a metastasis the balance might be shifted more towards basement membrane deposition. The tendency of a tumor to deposit basement membranes reflects the biological potential of the neoplasm. Basement membranes are deposited by stromal cells or by a concerted action of tumor and stromal cells. Differentiation in a carcinoma is modulated by factors in the extracellular matrix. Endocrine differentiation can be induced in vitro by native basement membranes but also by direct contact of the tumor cells with fibroblasts. Basic FGF is one of the extracellular matrix factors with differentiation inducing capacity. Expression of cell adhesion molecules and integrin receptors tends to be down-regulated in carcinoma cells. Alterations in the expression of these proteins might not be constitutive but rather modulated by the direct environment of the tumor cell and might not only include quantitative alterations but also changes in their cell surface distribution, causing or following loss of cell polarity.