CD163-positive cancer cells are potentially associated with high malignant potential in clear cell renal cell carcinoma

2017 ◽  
Vol 51 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Chaoya Ma ◽  
Hasita Horlad ◽  
Koji Ohnishi ◽  
Takenobu Nakagawa ◽  
Sohsuke Yamada ◽  
...  
2021 ◽  
pp. 1-11
Author(s):  
Zi-Bin Xu ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo ◽  
Yu-Hui Xia ◽  
...  

<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.


Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 509
Author(s):  
Giuseppe Lucarelli ◽  
Matteo Ferro ◽  
Davide Loizzo ◽  
Cristina Bianchi ◽  
Daniela Terracciano ◽  
...  

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.


Oncotarget ◽  
2018 ◽  
Vol 9 (28) ◽  
pp. 20058-20074 ◽  
Author(s):  
Lucile Broncy ◽  
Basma Ben Njima ◽  
Arnaud Méjean ◽  
Christophe Béroud ◽  
Khaled Ben Romdhane ◽  
...  

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lu Wang ◽  
Guang Yang ◽  
Danfeng Zhao ◽  
Jiaqi Wang ◽  
Yang Bai ◽  
...  

Abstract Background Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells. Methods The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined. Results CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR-19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103+ CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103+ exosomes were increased in blood samples from CCRCC patients with lung metastasis. Conclusions CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103+ acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103+ exosomes as a potential metastatic diagnostic biomarker. Graphical abstract ᅟ


2013 ◽  
Vol 5 (4) ◽  
pp. 274
Author(s):  
Jehonathan H. Pinthus H. Pinthus ◽  
Kaitlyn F. Whelan ◽  
Daniel Gallino ◽  
Jian-Ping Lu ◽  
Nathan Rothschild

Central to the malignant behaviour that endows cancer cells withgrowth advantage is their unique metabolism. Cancer cells canprocess nutrient molecules differently from normal cells and useit to overcome stress imposed on them by various therapies. Thismetabolic conversion is controlled by specific genetic mutationsthat are associated with activation of oncogenes and loss of tumoursuppressor proteins. Understanding these processes is importantas it can lead to the discovery of biomarkers that can predict theaggressiveness of the disease and its response to therapy, and evenmore importantly, to the development of novel therapeutics. A classictumour in this respect is clear-cell renal cell carcinoma (RCC). Inthis review, we will begin with a brief summary of normal cellularbioenergetic pathways, which will be followed by a descriptionof the characteristic metabolism of glucose and lipids in clear-cellRCC cells and its clinical implications. Data relating to the potentialeffect of dietary nutrients on RCC will also be reviewed alongwith potential therapies targeted at interrupting specific metabolicpathways in clear-cell RCC.Le métabolisme unique des cellules cancéreuses est au coeur ducomportement malin qui leur confère un avantage sur le plan de lacroissance. Les cellules cancéreuses peuvent traiter les moléculesde nutriment différemment des cellules normales et utilisent cesmolécules pour surmonter le stress imposé par les différents traitements.La conversion métabolique est contrôlée par des mutationsgénétiques précises associées à l’activation d’oncogènes et à laperte de protéines de suppression tumorale. Il est important debien saisir ces processus, car leur élucidation peut mener à ladécouverte de biomarqueurs permettant de prédire l’agressivité dela maladie et la réponse au traitement et, fait encore plus important,elle peut mener à la mise au point de nouveaux médicaments. À cetégard, l’hypernéphrome à cellules claires représente une tumeurclassique. Dans cet article, nous commençons par résumer brièvementles voies bioénergétiques cellulaires normales, puis nouspoursuivons avec une description du métabolisme caractéristiquedu glucose et des lipides dans les cellules de l’hypernéphrome àcellules claires et ses répercussions cliniques. Les données associéesà l’effet potentiel des nutriments sur l’hypernéphrome à cellulesclaires seront aussi passées en revue, ainsi que les thérapiesciblées potentielles visant l’interruption de voies métaboliquesparticulières dans l’hypernéphrome à cellules claires.


2019 ◽  
Vol 27 (9) ◽  
pp. 726-738 ◽  
Author(s):  
Qianqian Shi ◽  
Renfang Xu ◽  
Guanglai Song ◽  
Hao Lu ◽  
Dong Xue ◽  
...  

AbstractTumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.


2014 ◽  
Vol 192 (6) ◽  
pp. 1831-1841 ◽  
Author(s):  
Vanessa Galleggiante ◽  
Monica Rutigliano ◽  
Fabio Sallustio ◽  
Domenico Ribatti ◽  
Pasquale Ditonno ◽  
...  

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