Exosomes Derived from Cancer-Associated Fibroblasts Regulate Cell Progression in Clear-Cell Renal-Cell Carcinoma

Nephron ◽  
2021 ◽  
pp. 1-10
Author(s):  
Wenqiang Fu ◽  
Haihong Zhao ◽  
Yifei Liu ◽  
Honglin Nie ◽  
Bin Gao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Clear Cell ◽  
Cancer Associated Fibroblasts ◽  
Cell Renal Cell Carcinoma ◽  
Western Blot Assay

<b><i>Backgrounds:</i></b> Exosomes from multiple sources function as regulatory factors in progression of various tumors. However, studies on the impact of exosomes from cancer-associated fibroblasts (CAFs) on tumor-cell proliferation, migration, invasion, and cycle regulation in clear-cell renal-cell carcinoma (ccRCC) are still lacking. <b><i>Methods:</i></b> A Western blot assay was performed to test the exosome-related marker protein level in exosomes derived from CAFs and normal fibroblasts (NFs). A confocal microscope was utilized to observe the internalization of CAF- and NF-derived exosomes after coculturing with cancer cells. MTT, EdU, colony formation, and transwell assays were conducted to detect progression of cancer cells incubated with CAF-derived exosomes. A Western blot assay was also conducted to test expression levels of metastasis-associated proteins. Changes in cell apoptosis and cell cycle were measured by flow cytometry. <b><i>Results:</i></b> Expression of CAF-derived exosome-related marker proteins was higher than that from NFs. Exosomes derived from CAFs and NFs could enter into cancer cells smoothly and be internalized by cancer cells. After cancer cells were cocultured with CAF-derived exosomes, cell proliferation, migration, and invasion were notably enhanced, and cell apoptosis was reduced. Moreover, expression of fibronectin, N-cadherin, vimentin, MMP9, and MMP2 in cancer cells increased, while E-cadherin was decreased. Besides, the proportion of cancer cells in the S phase increased. <b><i>Conclusion:</i></b> CAF-derived exosomes are internalized into ccRCC cells and promote the progression of ccRCC.

scholarly journals Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 48 (3) ◽  
pp. 1075-1087 ◽  
Author(s):  
Yan Qu ◽  
Haibing Xiao ◽  
Wen Xiao ◽  
Zhiyong Xiong ◽  
Wenjun Hu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Proliferation And Metastasis

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

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.

scholarly journals Delivery of miR-224-5p by Exosomes from Cancer-Associated Fibroblasts Potentiates Progression of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yifei Liu ◽  
Wenqiang Fu ◽  
Xiaoning Cao ◽  
Shuopeng Li ◽  
Tianyu Xiong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Biological Information ◽  
Cancer Associated Fibroblasts ◽  
Cell Renal Cell Carcinoma ◽  
Transmission Electron ◽  
Marker Proteins ◽  
P Cells

Objectives. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Cancer-associated fibroblasts (CAFs) as the primary components of cancer stroma can affect tumor progression by secreting exosomes, while exosomes are carriers for proteins, nucleic acids, and other agents that responsible for delivery of biological information. Given this, exosomes derived from CAFs are emerging as promising biomarkers in clinical cancer diagnosis. Nevertheless, their role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. Methods. Here, we separated fibroblasts from ccRCC tissue, extracted exosomes, observed their morphology, and detected the expression of exosome marker proteins including Hsp70, CD9, and CD63. In the meantime, we labeled exosomes and performed coculture experiment to verify the delivery of miR-224-5p from CAFs to 769-P cells with exosomes as a carrier, so as to clarify the effect of CAF-derived exosomes on ccRCC cell malignant behaviors, as well as to discuss how miR-224-5p involves in above regulation. Results. Transmission electron microscopy was firstly applied, and it was noted that the exosomes we isolated were in normal range. Besides, Western blot also confirmed the presence of exosome marker proteins Hsp70, CD9, and CD63. Furthermore, coculture experiments were performed and the CAF-derived exosomes were observed to be able to facilitate the malignant behaviors of ccRCC cells, and the exosomal miR-224-5p could be internalized by ccRCC cells to participate in regulation of cell proliferation, migration, invasion, and apoptosis. Conclusion. To sum up, miR-224-5p can enter ccRCC cells via CAF-derived exosomes, in turn, promoting the malignant behaviors of ccRCC cells, which indicates that miR-224-5p has the potential severing as a therapeutic target for ccRCC.

The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma

2021 ◽  
pp. 1-11
Author(s):  
Zi-Bin Xu ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo ◽  
Yu-Hui Xia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Tumor Tissue ◽  
Transforming Growth Factor ◽  
Clear Cell ◽  
Tumor Promoter ◽  
Sequencing Data ◽  
Cell Renal Cell Carcinoma

<b><i>Background:</i></b> Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-β superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. <b><i>Methods:</i></b> The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin βE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin βE expression level and patient’s clinicopathological indices was evaluated. <b><i>Results:</i></b> In the normal renal tissue, inhibin βE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin βE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin βE in the tumor tissue and tumor grade. Patients with a lower inhibin βE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. <b><i>Conclusions:</i></b> INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

scholarly journals Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 509
Author(s):  
Giuseppe Lucarelli ◽  
Matteo Ferro ◽  
Davide Loizzo ◽  
Cristina Bianchi ◽  
Daniela Terracciano ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Renal Cell Carcinoma ◽  
Lipid Metabolism ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Chemotherapy Resistance ◽  
Neoplastic Tissue ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase (SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.

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