Heparanase expression and glycosaminoglycans profile in renal cell carcinoma

Abstract

Abbreviations & Acronyms CS = chondroitin sulfate DS = dermatan sulfate ECM = extracellular matrix GAG = glycosaminoglycan GAPDH = glyceraldehydes-3-phosphate dehydrogenase HA = hyaluronic acid HS = heparan sulfate mRNA = messenger ribonucleic acid RCC = renal cell carcinoma RNA = ribonucleic acid Abstract: A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative realtime reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

Glycosaminoglycan Profiling in Patients’ Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma

“…Notably, a recent characterization of the GAG profile in early-stage ccRCC tissues was strongly correlated with the here-uncovered regulatory program (Ucakturk et al, 2016). In addition, a previous study examined CS/HS concentrations in early-stage ccRCC tissue samples (Batista et al, 2012), and re-elaboration of these data to emphasize the CS/HS ratio delineated a consistent trend ( Figure S5). Overall, these data and our study were suggestive of an active and early role for ccRCC in de novo GAG production, likely stemming from gene expression regulation.…”

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma

“…Changes in the profile of GAG sulfates are related to the development of many illnesses, such as cancer, inflammatory diseases, degenerative diseases, as well as healing processes. 22,25 The study of extracellular components, such as proteoglycans, fibrous proteins, glycoproteins, metalloproteases, and glycosidases, can shed light on the molecular changes directly related to the development of such diseases. 16,24,26 …”

Acquisition of Anoikis Resistance Up-Regulates Syndecan-4 Expression in Endothelial Cells

“…Most studies investigating heparanase have focused on its regulated expression at different stages of cancer progression, and its overexpression in tumor cells has also been reported to correlate with metastatic potential and poorer prognosis [81] , [82] . Heparanase and glycosaminoglycans can modulate initial events of renal cell carcinoma development [83] . In bone tissue, heparanase-1 overexpression creates a complex phenotype that typically results in osteogenesis and increased bone mass [84] .…”