Prognostic factors in renal cell and bladder cancer

Brussel, Van; Mickisch,

doi:10.1046/j.1464-410x.1999.00120.x

Cited by 48 publications

(31 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In analogy, the cadherin expression pattern of RCC tumor cells could represent a prognostic marker since other biomolecular factors previously analyzed, e.g., grade of nuclear pleomorphism, morphometric analysis, proliferation rate, p53 overexpression, expression of renal antigens and specific genetic alterations, have not been proven to be reliable for the assessment of disease outcome in RCC. 41 In conclusion, our data suggest that distinct type II cadherins may play a pathogenic role in RCC development. In particular, cadherin-8 might be involved in both the process of kidney morphogenesis and tumorigenesis in some types of RCC.…”

Section: Expression Of Cadherin-8 In Fetal Kidneymentioning

confidence: 59%

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

Blaschke

Mueller

Marković-Lipkovski

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

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...

show abstract

Section: Expression Of Cadherin-8 In Fetal Kidneymentioning

confidence: 59%

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

Blaschke

Mueller

Marković-Lipkovski

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…High-grade, invasive bladder tumours often show genetic aberrations including overexpression of HER2/ neu and EGFR associated with an increased frequency of progression to an advanced tumour stage and poor survival. Low-grade bladder tumours are noninvasive, but more than 70% of patients will have at least one recurrence after initial treatment (Van Brussel and Mickisch, 1999). Overexpression of EGFR is correlated with a higher recurrence rate and higher tumour progression.…”

Section: Discussionmentioning

confidence: 99%

Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion

2003

View full text Add to dashboard Cite

Signalling through G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) is involved in the regulation of essential cellular processes and its deregulation is associated with tumorigenesis in vitro and in vivo. We investigated pathophysiological processes that are regulated by GPCR pathways in human kidney and bladder cancer cell lines. Our results show that GPCR ligands induce tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as well as downstream signalling events such as recruitment of the adapter protein Shc and activation of the mitogen-activated protein kinases (MAPK) ERK1/2, JNK and p38. Moreover, we report that the EGFR transactivation signal involves the EGFR ligands amphiregulin, HB-EGF and TGFa as well as the metalloproteinases ADAM 10, 15 and 17, depending on the cellular system. Finally, we demonstrate that EGFR transactivation is part of a regulatory system that modulates the migratory and invasive behaviour of kidney and bladder cancer cells. In conclusion, our findings demonstrate that metalloproteinase-mediated transactivation of the EGFR is a key mechanism of the cellular signalling network that promotes MAPK activation as well as tumour cell migration and invasion in response to a variety of physiologically relevant GPCR ligands, and therefore represents a novel target for cancer intervention strategies.

show abstract

“…Within the United States, TCC is twice as common among White people compared with Blacks, and incidence and mortality directly increases with age (1,6). Still, the best established and routinely used clinical markers to predict prognosis are depth of tumor invasion, presence or absence of lymph node and distant metastases, and tumor differentiation (7). Tumor progression is thought to result from the accumulation of multiple genetic alterations, including the activation of oncogenes, loss of distinct chromosomal regions, and inactivation of tumor suppressor genes, such as p53 and Rb (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

The T393C Polymorphism of the Gαs Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer

Frey¹,

Eisenhardt²,

Lümmen³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The G protein GAs pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding GAs as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the bladder, we genotyped the synonymous T393C polymorphism in 254 patients with TCC (minor allele frequency: 0.43) to examine a potential association between genotypes and disease progression. Using Kaplan-Meier estimates to calculate 5-year probabilities of follow-up, we could show that progressionfree survival, metastasis-free survival, and cancer-specific survival was significantly increased in TT genotypes (56%, 84%, 82%) compared with CC genotypes (35%, 53%, 58%). In multivariate Cox proportional hazard analysis, the T393C polymorphism was an independent prognostic factor for clinical outcome. Homozygous CC patients were at highest risk for progression [odds ratio (OR), 1.94; P = 0.020], metastasis (OR, 3.49; P = 0.005), and tumor-related death (OR, 2.49; P = 0.031) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. Real-time PCR analysis of urothelial tumor tissue as well as adipose and heart tissue revealed that GAs mRNA expression was highest in TT genotypes, indicating a proapoptotic effect in these genotypes. In conclusion, the GNAS1 T393C status associated with differential GAs mRNA expression is a novel independent prognostic marker for clinical outcome supporting a functional role of GAs in bladder cancer progression. (Cancer Epidemiol Biomarkers Prev 2005;14(4):871 -7)

show abstract

Prognostic factors in renal cell and bladder cancer

Cited by 48 publications

References 68 publications

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

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

Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion

The T393C Polymorphism of the Gαs Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer

Contact Info

Product

Resources

About