Renal cell carcinomas (RCCs) represent 3% of all adult malignancies and are often associated with poor prognosis due to early metastasis and limited beneficial effects of current therapeutic modalities. 1 Most of these tumors originate from the proximal tubule. According to cell morphology and growth pattern, 3 main histologic tumor types can be distinguished, including clear cell carcinoma, papillary renal carcinoma and chromophobe RCC. 2 Several factors that may contribute to the process of malignant cell transformation in RCC have previously been characterized, including physical agents, chemical agents, habits, genetics (chromosomal rearrangement) and end-stage renal disease. 3 However, the pathogenic mechanisms that promote tumor progression, i.e., tumor invasion and metastasis, still have to be defined. There is accumulating evidence that cadherins may be involved in the pathogenesis of various human carcinomas by modulating celladhesive properties.The cadherin superfamily represents a group of cell-surface glycoproteins involved in cell recognition, cell signaling, cell communication, morphogenesis as well as angiogenesis and includes the groups of classic cadherins, desmosomal cadherins, protocadherins, 7TM-cadherins and T-cadherin. 4 The human classic cadherins are a group of cell-surface molecules mediating Ca 2Ï© -dependent cell adhesion by homo-or heterophilic interaction. These proteins, m.w. approximately 120 -130 kDa, are composed of an extracellular domain with 5 subdomains, each of which contains a cadherin-specific motif at the N-terminal site, a single transmembrane domain and a rather short and highly conserved cytoplasmic domain at the C-terminal site. The adhesive action of cadherins depends on the presence of Ca 2Ï© and on the function of the intracellular domain. 5 Cadherins are linked to the actin filament network through cytoplasmic interactions with catenins. These catenins regulate cadherin-mediated cell-cell adhesion. 6 In addition, these molecules may function as a downstream transcriptional activator. 7,8 More than 12 different molecules of the classic human cadherins have been identified so far by cDNA cloning. With respect to sequence homology and conservation of several amino acid residue motifs in the extracellular domain, Suzuki et al. 9 first proposed subdividing the classic human cadherins into 2 subgroups: type I (E-, N-and P-cadherins, cadherin-4) and type II (cadherins 5-15). Cadherin-8, a type II cadherin, was cloned by Tanihara et al. 10 and is characterized by strong sequence homology with the classical type I cadherins. 11 In mice, cadherin-8 expression is restricted to the developing CNS and thymus. 12,13 As has been demonstrated for type I cadherins, type II cadherins interact with âŁ-and â€-catenins. 14 Using an L-fibroblast cDNA transfection system and a long-term cell-aggregation assay, Shimoyama et al. 15 clearly demonstrated that all 8 type II cadherins exhibited cell-cell binding activity comparable to that of E-cadherin. Heterophilic interactions among the type I...