EXTRACELLULAR-MATRIX IN RENAL-CELL CARCINOMAS

Extracellular matrix (ECM) may be divided into interstitial matrix and the basement membrane (BM). ECM influences a variety of epithelial ce ll behaviours, including proliferation, differentiation, and morphogen esis, maybe most widely studied in kidney morphogenesis. In carcinomas , including renal cell carcinomas (RCCs), these properties and interac tions of cells with interstitial matrix and BM are disturbed. As a car cinoma with a tendency to spread to distant sites, RCC is an interesti ng target for the study of epithelial-stromal interactions. Among inte rstitial collagens, type VT collagen appears to be widely distributed in RCCs. Also EDA-fibronectin (EDA-Fn) as well as tenascin-C (Tn) are important stromal components especially in poorly differentiated carci nomas. BMs of RCC islets and those of tumor blood vessel endothelia ma y merge in poorly differentiated carcinomas. As a dynamic component of BMs, laminins (Ln) are important in kidney development and RCC progre ssion. Type IV collagen and nidogen, other components of BMs in RCCs, are produced by stromal as well as epithelial cells. ECM proteins may function in RCC progression by binding and regulating the activity of growth factors e.g. transforming growth factor beta 1 and basic fibrob last growth factor. Also the expression of cell surface receptors for ECM is disturbed in RCCs. At least a, integrin (Int) and CD44 emerge i n renal epithelial cells during malignant transformation. Papillary re nal neoplasms differ from RCCs by cell adhesion receptor expression an d BM composition as well as by ECM avascularity and capacity to bind g rowth factors, thus suggesting a distinct property for this renal tumo r.