scholarly journals Metabolomic Analysis to Elucidate Mechanisms of Sunitinib Resistance in Renal Cell Carcinoma

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Tomonori Sato ◽  
Yoshihide Kawasaki ◽  
Masamitsu Maekawa ◽  
Shinya Takasaki ◽  
Kento Morozumi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Energy Metabolism ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Treatment Resistance ◽  
Tca Cycle ◽  
Glutamine Uptake

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

scholarly journals Identification Of Gene Signature For Renal Cell Carcinoma-Associated Fibroblasts Mediating Cancer Progression And Affecting Prognosis

2020 ◽  
Author(s):  
Bitian Liu ◽  
Xiaonan Chen ◽  
Yunhong Zhan ◽  
Bin Wu ◽  
Shen Pan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Single Cell ◽  
Clinical Significance ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Gene Signature ◽  
Pathological Grade ◽  
Single Cell Sequencing

Abstract Background: Cancer-associated fibroblasts (CAFs) are most abundant in stroma and are critically involved in cancer progression. However, the specific signature of CAFs and related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Methods: In this work, methods using recognized gene signatures were employed to roughly assess the infiltration level of the stroma and CAFs in RCC based on the data in The Cancer Genome Atlas. Weighted gene co-expression network analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify specific markers. A comparison of fibroblast versus urothelial carcinoma cell lines and correlation with previously reported CAF markers were performed to demonstrate the specific expressed of the gene signature. The gene signature was used to compare fibroblast infiltration of each sample through single sample gene set enrichment analysis, and the clinical significance of fibroblasts was analyzed via Cox risk assessment and the chi-square test. Finally, we used validation data to verify the clinical significance of the fibroblast gene signature in RCC. Results: Roughly calculated tumor matrix and CAF levels were significantly higher in kidney cancer than in normal tissues. More than 85% of fibroblast-specific markers identified by WGCNA were consistent with markers obtained via single-cell sequencing. These markers were more highly expressed in fibroblast cell lines and were significantly correlated with canonical CAFs makers. Data validation also showed that CAFs were significant correlation with survival and pathological grade. Conclusions: In summary, our findings indicate that the gene signature potentially serves as a biomarker of CAFs in RCC and that infiltration of fibroblasts in RCC is an independent prognostic factor associated with pathological grade and stage of tumor. The ability to recognize specific CAF markers using WGCNA is comparable to single-cell sequencing.

Identification of an appropriate cell line for the renal cell carcinoma model

2020 ◽  
Author(s):  
In Youb Chang ◽  
Takbum Ohn ◽  
Daeun Moon ◽  
Young Hee Maeng ◽  
Bo Gun Jang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Renal Cell ◽  
Tissue Microarrays ◽  
Future Research ◽  
Proximal Tubule Cells

Abstract Background Although renal cell carcinoma (RCC) is known to be susceptible to ferroptosis, we found primary RCC cells showed resistance to ferroptosis and aimed to investigate a feasible candidate for an appropriate cell line for the RCC model. Methods Glutathione peroxidase 4 (GPX4) immunostaining was adopted in the RCC tissue microarrays. Normal human proximal tubule cells (HK-2) and RCC cell lines were used for the MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of athymic Balb/c-nude mice. Results GPX4 immunostaining showed low intensity compared to the normal kidney, which coincided with the ferroptosis-susceptibility of RCC. Primary RCC cell lines (Caki-2, SNU-333, SNU-349, and SNU-1272) showed resistance to 5-fluorouracil and a GPX4 inhibitor compared to the HK-2 cells and to metastatic RCC cells (Caki-1). The Caki-2 cells showed increased GPX4 and xCT, and the SNU-333 cells showed increased ferritin heavy chain (FTH1) compared to the other RCC cells. The Caki-2 cells showed increased aSMA, fibronectin, vimentin, and SNAIL, and the SNU-333 cells showed increased aSMA, E-cadherin, and EpCAM. The Caki-2 cells showed increased Sox-2 and CD105, and the SNU-333 cells showed increased c-Myc and Lgr5. The Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic RCC masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, consistent with the diagnostic criteria for RCC. Conclusions The primary RCC cell lines used in this study were more resistant to ferroptosis and 5-fluorouracil, and the SNU-333 cells showed tumor-initiating capacities in vitro and in vivo. These results suggest that SNU-333 might be suitable as a orthotopic RCC model for future research.

scholarly journals MicroRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene

2017 ◽  
Vol 242 (12) ◽  
pp. 1299-1305 ◽  
Author(s):  
Xiang Sun ◽  
Longhua Lou ◽  
Kezhao Zhong ◽  
Lijuan Wan
Keyword(s):  
Renal Cell Carcinoma ◽  
Drug Resistance ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Luciferase Reporter ◽  
Multi Drug Resistance

Renal cell carcinoma (RCC) is a malignant tumor, which severely threatens human’s life, moreover, the multi-drug resistance (MDR) under RCC undoubtedly strengthen the difficulties in the treatment. MiR-451 has been considered to play an important role in regulation of MDR in several cancers, but the role of it in MDR of RCC has not been explored. This study aims to explore the mechanism of miR-451 as a target to regulate chemotherapy resistance, which is crucial for further exploring novel therapy for RCC. Two human cell lines (ACHN and GRC-1) were performed in this study and adriamycin (ADM) was used to construct MDR cell lines. qRT-PCR was used to determine the mRNA expression of miR-451 and ATF-2. Weston blot was used to determine protein expression. MTT assay and flow cytometry were used for assessing cell viability and apoptosis, individually. Luciferase reporter assay was used to detect the targeting of miR-451 and ATF-2. Results presented that the expression of miR-451 was higher in low MDR cell line (ACHN) comparing with the high MDR cell line (GRC-1), while the expression of ATF-2 revealed an opposite results. MiR-451 targeted ATF-2 and regulated its expression. Overexpression of miR-451 strengthened drug resistance, decreased cell viability, and increased cell apoptosis of GRC-1 pretreated by ADM, while overexpressed ATF-2 reversed the effect induced by miR-451 overexpression. Then miR-451 knockdown improved drug susceptibility, decreased cell apoptosis, and increased cell viability of ACHN induced by ADM, however, ATF-2 suppression reversed the low rate of cell apoptosis and high rate of cell viability induced by miR-451 knockdown. Our results revealed that miR-451 regulates the drug resistance of RCC by targeting ATF-2 gene, which might be critical for overcoming MDR in RCC patients. Impact statement This is the first study to emphasize the expression of miR-451 on regulating multi-drug resistance (MDR) in renal cell carcinoma (RCC). Our study found that miR-451 regulates the drug resistance of RCC by targeting ATF-2, which might be critical for overcoming MDR in RCC patients. This study not only provides solid theory foundation for the clinical therapy, but also offers unique insights for the further RCC research. Furthermore, the study helps us to understand the mechanism of MDR, which was crucial for identifying the chemoresistance on several related tumors.

scholarly journals Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines

2021 ◽  
Author(s):  
Youfeng Yang ◽  
Christopher J. Ricketts ◽  
Cathy D. Vocke ◽  
J. Keith Killian ◽  
Hesed M. Padilla‐Nash ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Carcinoma Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Renal Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

2011 ◽  
Vol 58 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Seong H Yoo ◽  
Kyoungbun Lee ◽  
Ji Y Chae ◽  
Kyung C Moon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

2006 ◽  
Vol 103 (27) ◽  
pp. 10391-10396 ◽  
Author(s):  
A. E. Krambeck ◽  
R. H. Thompson ◽  
H. Dong ◽  
C. M. Lohse ◽  
E. S. Park ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Tumor Vasculature

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

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