The role of hyaluronan in renal cell carcinoma

Jin, Chen; Zong, Yunfeng

doi:10.3389/fimmu.2023.1127828

Cited by 8 publications

(3 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with observations performed on human patients. In the healthy kidney, HA is absent in the cortex, while is mainly produced and secreted in medullary stroma [ 56 , 57 ]. This is in sharp contrast with RCC tumors in which the presence of cellular hyaluronan correlates with higher tumor grades and poor prognosis for patients.…”

Section: Discussionmentioning

confidence: 99%

Renal cancer secretome induces migration of mesenchymal stromal cells

Popławski,

Zarychta-Wiśniewska,

Burdzińska

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Advanced renal cell carcinoma (RCC) is therapeutically challenging. RCC progression is facilitated by mesenchymal stem/stromal cells (MSCs) that exert remarkable tumor tropism. The specific mechanisms mediating MSCs’ migration to RCC remain unknown. Here, we aimed to comprehensively analyze RCC secretome to identify MSCs attractants. Methods Conditioned media (CM) were collected from five RCC-derived cell lines (Caki-1, 786-O, A498, KIJ265T and KIJ308T) and non-tumorous control cell line (RPTEC/TERT1) and analyzed using cytokine arrays targeting 274 cytokines in addition to global CM proteomics. MSCs were isolated from bone marrow of patients undergoing standard orthopedic surgeries. RCC CM and the selected recombinant cytokines were used to analyze their influence on MSCs migration and microarray-targeted gene expression. The expression of genes encoding cytokines was evaluated in 100 matched-paired control-RCC tumor samples. Results When compared with normal cells, CM from advanced RCC cell lines (Caki-1 and KIJ265T) were the strongest stimulators of MSCs migration. Targeted analysis of 274 cytokines and global proteomics of RCC CM revealed decreased DPP4 and EGF, as well as increased AREG, FN1 and MMP1, with consistently altered gene expression in RCC cell lines and tumors. AREG and FN1 stimulated, while DPP4 attenuated MSCs migration. RCC CM induced MSCs’ transcriptional reprogramming, stimulating the expression of CD44, PTX3 and RAB27B. RCC cells secreted hyaluronic acid (HA), a CD44 ligand mediating MSCs’ homing to the kidney. AREG emerged as an upregulator of MSCs’ transcription. Conclusions Advanced RCC cells secrete AREG, FN1 and HA to induce MSCs migration, while DPP4 loss prevents its inhibitory effect on MSCs homing. RCC secretome induces MSCs’ transcriptional reprograming to facilitate their migration. The identified components of RCC secretome represent potential therapeutic targets. Graphical abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Renal cancer secretome induces migration of mesenchymal stromal cells

Popławski,

Zarychta-Wiśniewska,

Burdzińska

et al. 2023

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…It is the seventh most common cancer in men and the ninth most common cancer in women, accounting for 3%–4% of all adult malignancies. 1 , 2 , 3 Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype, accounting for approximately 75% of RCCs, is characterized by a high propensity for metastasis and immune infiltration and is associated with a poorer prognosis compared to other RCC subtypes. 4 , 5 , 6 , 7 Since the clinical benefit of chemoradiotherapy is inferior to that of surgical treatment in ccRCC, surgical treatment is the main option for patients.…”

Section: Introductionmentioning

confidence: 99%

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Yang,

Zhang,

Zhan

et al. 2024

Cancer Medicine

View full text Add to dashboard Cite

BackgroundExosomes play a crucial role in intercellular communication in clear cell renal cell carcinoma (ccRCC), while the long non‐coding RNAs (lncRNAs) are implicated in tumorigenesis and progression.AimsThe purpose of this study is to construction a exosomes‐related lncRNA score and a ceRNA network to predict the response to immunotherapy and potential targeted drug in ccRCC.MethodsData of ccRCC patients were obtained from the TCGA database. Pearson correlation analysis was used to identify eExosomes‐related lncRNAs (ERLRs) from Top10 exosomes‐related genes that have been screened. The entire cohort was randomly divided into a training cohort and a validation cohort in equal scale. LASSO regression and multivariate cox regression was used to construct the ERLRs‐based score. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and drug susceptibility between the high‐ and low‐risk groups were also investigated. Finally, the relevant ceRNA network was constructed by machine learning to analyze their potential targets in immunotherapy and drug use of ccRCC patients.ResultsA score consisting of 4ERLRs was identified, and patients with higher ERLRs‐based score tended to have a worse prognosis than those with lower ERLRs‐based score. ROC curves and multivariate Cox regression analysis demonstrated that the score could be considered as a risk factor for prognosis in both training and validation cohorts. Moreover, patients with high scores are predisposed to experience poor overall survival, a larger prevalence of advanced stage (III‐IV), a greater tumor mutational burden, a higher infiltration of immunosuppressive cells, and a greater likelihood of responding favorably to immunotherapy. The importance of EMX2OS was determined by mechanical learning, and the ceRNA network was constructed, and EMX2OS may be a potential therapeutic target, possibly exerting its function through the EMX2OS/hsa‐miR‐31‐5p/TLN2 axis.ConclusionsBased on machine learning, a novel ERLRs‐based score was constructed for predicting the survival of ccRCC patients. The ERLRs‐based score is a promising potential independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics. Meanwhile, we screened out key lncRNAEMX2OS and identified the EMX2OS/hsa‐miR‐31‐5p/TLN2 axis, which may provide new clues for the targeted therapy of ccRCC.

show abstract

“…The most common GAGs in urothelium and endothelial glycocalyx are hyaluronic acid (HA), chondroitin sulfate (CS), and heparin ( 6 , 17 ). Several pathogenic bacteria produce enzymes that digest GAGs, which can destroy barrier functions, provide a carbohydrate source for microbial growth, and alter the innate immune response either by promoting inflammation or disrupting inflammatory signaling.…”

Section: Introductionmentioning

confidence: 99%

Function and contribution of two putative Enterococcus faecalis glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection

Johnson,

Shipman,

Hunt

et al. 2024

Infect Immun

View full text Add to dashboard Cite

Enterococcus faecalis is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of E. faecalis infection is frequently complicated by multi-drug resistance. Based on protein homology, E. faecalis encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB). In other Gram-positive pathogens, hyaluronidases have been shown to contribute to tissue damage and immune evasion, but the function in E. faecalis has yet to be explored. Here, we show that both hylA and hylB contribute to E. faecalis pathogenesis. In a CAUTI model, Δ hylA exhibited defects in bladder colonization and dissemination to the bloodstream, and Δ hylB exhibited a defect in kidney colonization. Furthermore, a Δ hylA Δ hylB double mutant exhibited a severe colonization defect in a model of bacteremia while the single mutants colonized to a similar level as the wild-type strain, suggesting potential functional redundancy within the bloodstream. We next examined enzymatic activity, and demonstrate that HylB is capable of digesting both hyaluronic acid (HA) and chondroitin sulfate in vitro , while HylA exhibits only a very modest activity against heparin. Importantly, HA degradation by HylB provided a modest increase in cell density during the stationary phase and also contributed to dampening of lipopolysaccharide-mediated NF-κB activation. Overall, these data demonstrate that glycosaminoglycan degradation is important for E. faecalis pathogenesis in the urinary tract and during bloodstream infection.

show abstract

The role of hyaluronan in renal cell carcinoma

Cited by 8 publications

References 173 publications

Renal cancer secretome induces migration of mesenchymal stromal cells

Renal cancer secretome induces migration of mesenchymal stromal cells

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Function and contribution of two putative Enterococcus faecalis glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection

Contact Info

Product

Resources

About