Cadherin-6, a Cell Adhesion Molecule Specifically Expressed in the Proximal Renal Tubule and Renal Cell Carcinoma

Paul, R.; Ewing, Charles M.; Robinson, J. C.; Marshall, Fray F.; Johnson, Keith R.; Wheelock, Margaret J.; Isaacs, William B.

doi:10.1097/00005392-199805000-00147

Cited by 38 publications

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“…Overexpression of other members of the cadherin superfamily, such as cadherin 6, have been described in several tumours including RCC (Shimoyama et al, 1995), and the aberrant expression of cadherin-6 correlates with poor prognosis (Paul et al, 1997;Shimazui et al, 2000). Vimentin, found in this study by Atlas blot hybridization and reported before by Moch et al (1999) to be aberrantly expressed in RCC, has been repeatedly shown to correlate with high metastatic potential (Thompson et al, 1994;Hendrix et al, 1996).…”

Section: Discussionsupporting

confidence: 67%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

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Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 1.4% of cancer-related deaths (Reis and Faria, 1994). The prognosis of RCC remains poor. One third of the patients already have metastases when first consulting the hospital. Another 30-40% of patients develop metastases after surgical excision of the primary tumour (Ravaud and Debled, 1999). RCC are radioresistant (Nieder et al, 1996) and more than 80% are chemoresistant (Mickisch, 1994). Since RCC are presumed to be immunogenic, several clinical trials are exploring the efficacy of cytokines, mainly interleukin 2 (IL2) and/or interferon-α (IFNα), and the transfer of lymphokine-activated killer cells (Hofmockel et al, 1997;Bukowski, 2000;Hoffman et al, 2000). Despite these new options, the median survival time of patients with metastatic disease still remains only 6-8 months and the overall 5-year survival rate is less than 5% (Moch et al, 2000;Motzer and Russo, 2000). Thus, there is an urgent requirement for alternative therapeutic modalities.The current strategy is to design therapeutic approaches based on specific biological features of each tumour type. These include (i) the aberrant expression of genes which can be recognized by the immune system as foreign (Pawelec et al, 1999;Wang and Rosenberg, 1999;Bremers and Parmiani, 2000); (ii) gene products related to the formation of new blood vessels (neoangiogenesis), since they are essential for tumour expansion and metastatic settlement (Harris and Thorgeirsson, 1998;Kerbel, 2000;Rosen, 2000) and (iii) the altered expression of adhesion molecules, matrix-degrading enzymes, their receptors and inhibitors, which are a further requisite of metastatic spread (Huang et al, 1997;Yu et al, 1997).Several technique enable the identification of tumour markers. Subtractive hybridization (Lamar and Palmer, 1984; Kunkel et al, 1985;Kuang et al, 1998), differential display reverse transcription-polymerase chain reaction (DD RT-PCR; Liang and Pardee, 1992) and hybridization of cDNA microarrays (reviewed in Khan et al, 1999) are frequently used to compare the expression patterns between tumour and normal tissue. Other approaches, such as serological screening (SEREX;Sahin et al, 1995) and screening of cytotoxic T lymphocyte activity against an autologous tumour cell line (De Plaen et al, 1988), are especially focused on the identification of immunogenic tumour molecules.We have described recently the successful use of SSH using matched RCC and normal kidney tissue . In this study, we randomly selected 16 genes, which by SSH appeared to be differentially expressed. Differential expression of 9 of these 16 genes could be verified by Northern blot analysis. 2 of the 9 genes appeared to be novel. From the remaining 7 genes, expression of 5 had been associated with the malignant phenotype. To substantiate that SSH is a suitable method for the identification of differentially expressed genes, we performed a SSH with an additional pair of normal renal and RCC tissue and compared the validity of SSH ...

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Section: Discussionsupporting

confidence: 67%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

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“…E-cadherin expression is restricted to the distal tubules and collecting ducts of the human kidney, whereas N-cadherin and cadherin-6 expression are found on proximal tubules (Nouwen et al, 1993;Paul et al, 1997). Cadherin-8 can only be detected on developing tubular structures (Blaschke et al, 2002).…”

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Expression of Ksp-cadherin during kidney development and in renal cell carcinoma

et al. 2005

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Cadherins are a large family of cell -cell adhesion molecules acting in a homotypic, homophilic manner that play an important role in the maintenance of tissue integrity. In the human kidney, several members of the cadherin family (including E-and N-cadherin, cadherin-6, -8 and -11) are expressed in a controlled spatiotemporal pattern. Cadherin-16, also called kidney-specific (Ksp-) cadherin, is exclusively expressed in epithelial cells of the adult kidney. In renal cell carcinomas (RCCs), which are considered to originate from epithelial kidney tubular cells, a complex pattern of cadherin expression can be observed, but Ksp-cadherin expression has not been analysed so far. In the present study, we show that the expression of Ksp-cadherin is completely abrogated in RCCs. Whereas Kspcadherin can be detected at later stages of tubulogenesis during human renal development and in the distal tubules of adult kidneys, no expression was found by immunohistochemistry or Western blot analysis in RCC tumour tissues and several RCC cell lines. However, despite the lack of protein expression, mRNA synthesis of Ksp-cadherin could be detected by reverse transcriptasepolymerase chain reaction analysis in all RCC tissues and most of the RCC cell lines studied, although at a reduced level. The loss of Ksp-cadherin protein was only observed in the malignant part of the tumour kidneys, whereas in the normal part of the affected kidneys Ksp-cadherin expression was clearly detected. These results indicate a downregulation of Ksp-cadherin in RCC and suggest a role for this cell adhesion molecule in tumour suppression.

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“…20 In RCC, a complex pattern of cadherin expression has been demonstrated. 21 In normal renal tissue, the proximal tubular cells express mainly cadherin-6 22 and N-cadherin, whereas expression of E-cadherin is restricted to the epithelial cells of the distal tubules and collecting ducts. 23 The majority of RCCs express N-cadherin and cadherin-6, indicating that most of them originate from the proximal tubules, whereas E-cadherin is expressed to a lower extent by renal tumors; however, overlapping E-and Ncadherin expression patterns have also been detected.…”

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“…21 In addition, RCC tumor invasion and progression of disease appear to be closely related to altered cadherin expression. A strong association between cadherin-6 expression and RCC progression has been detected, 22 indicating that alterations in cadherin expression may serve as prognostic markers for these epithelial tumors. 24 Although many cadherins have been identified, the tissue distribution and functional properties of the type II cadherins in RCC have not been studied in detail.…”

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Expression of cadherin‐8 in renal cell carcinoma and fetal kidney

Blaschke

Mueller

Marković-Lipkovski

et al. 2002

Intl Journal of Cancer

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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 2ϩ -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 2ϩ 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 ␣-and ␤-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...

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Cadherin-6, a Cell Adhesion Molecule Specifically Expressed in the Proximal Renal Tubule and Renal Cell Carcinoma

Cited by 38 publications

References 0 publications

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Expression of Ksp-cadherin during kidney development and in renal cell carcinoma

Expression of cadherin‐8 in renal cell carcinoma and fetal kidney

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