scholarly journals ACE2 in tumor cells and tumor vasculature: Negligible intercellular transfer from cancer cells into endothelial cells

2021 ◽  
Vol 2 ◽  
pp. 3
Author(s):  
Zhi-Jie Liu ◽  
Yan Mei ◽  
Jiang-Li Lu ◽  
Jia-Bin Lu ◽  
Yun Cao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Gastric Adenocarcinoma ◽  
Renal Cell ◽  
Colorectal Adenocarcinoma ◽  
Tumor Vasculature ◽  
Intercellular Transfer

Cancer patients are more susceptible to severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Angiotensin-converting enzyme 2 (ACE2) is the functional host receptor for SARS-CoV-2 entering into human cells. Bioinformatics’ analyses have revealed that ACE2 is upregulated in some cancer cells. In the present study, we evaluated ACE2 protein expression levels in several common malignancies compared to non-cancerous normal tissues. ACE2 expression was elevated in colorectal adenocarcinoma, pancreatic adenocarcinoma, gastric adenocarcinoma, and papillary renal cell carcinoma cancer. Yet, it was suppressed in chromophobe renal cell carcinoma, testicular germ cell tumors, and papillary thyroid carcinoma. Two tumor tissue microarrays were used to evaluate the prognostic value of ACE2 expression in patients with gastric adenocarcinoma, and colorectal adenocarcinoma without COVID-19. No significant survival benefit was found for patients with overexpression of ACE2 in the tumor. In the tumor vasculature, ACE2 expression was observed in only 54% of the tumor micro-vessels. Using an in vitro co-culture of endothelial cells and tumor cells overexpressing fusion protein ACE2-red fluorescent protein, we did not observe any clear and convincing intercellular transfer of ACE2 from cancer cells into endothelial cells. In summary, alteration of ACE2 expression was found in common malignancies, but there is no evidence of intercellular transfer of ACE2 from cancer cells to endothelial cells.

scholarly journals Transglutaminase 2-Mediated p53 Depletion Promotes Angiogenesis by Increasing HIF-1α-p300 Binding in Renal Cell Carcinoma

2020 ◽  
Vol 21 (14) ◽  
pp. 5042
Author(s):  
Seon-Hyeong Lee ◽  
Joon Hee Kang ◽  
Ji Sun Ha ◽  
Jae-Seon Lee ◽  
Su-Jin Oh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Nuclear Translocation ◽  
Xenograft Model ◽  
Transglutaminase 2 ◽  
P300 Binding

Angiogenesis and the expression of vascular endothelial growth factor (VEGF) are increased in renal cell carcinoma (RCC). Transglutaminase 2 (TGase 2), which promotes angiogenesis in endothelial cells during wound healing, is upregulated in RCC. Tumor angiogenesis involves three domains: cancer cells, the extracellular matrix, and endothelial cells. TGase 2 stabilizes VEGF in the extracellular matrix and promotes VEGFR-2 nuclear translocation in endothelial cells. However, the role of TGase 2 in angiogenesis in the cancer cell domain remains unclear. Hypoxia-inducible factor (HIF)-1α-mediated VEGF production underlies the induction of angiogenesis in cancer cells. In this study, we show that p53 downregulated HIF-1α in RCC, and p53 overexpression decreased VEGF production. Increased TGase 2 promoted angiogenesis by inducing p53 degradation, leading to the activation of HIF-1α. The interaction of HIF-1α and p53 with the cofactor p300 is required for stable transcriptional activation. We found that TGase 2-mediated p53 depletion increased the availability of p300 for HIF-1α-p300 binding. A preclinical xenograft model suggested that TGase 2 inhibition can reverse angiogenesis in RCC.

scholarly journals The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids

2020 ◽  
Vol 11 ◽  
pp. 204173142092059
Author(s):  
Katerina Stamati ◽  
Patricia A Redondo ◽  
Agata Nyga ◽  
Joana B Neves ◽  
Maxine GB Tran ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Three Dimensional ◽  
Carcinoma Cells

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.

scholarly journals Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

2008 ◽  
Vol 88 (9) ◽  
pp. 962-972 ◽  
Author(s):  
Harriet M Kluger ◽  
Summar F Siddiqui ◽  
Cesar Angeletti ◽  
Mario Sznol ◽  
William K Kelly ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Vegf Receptors

scholarly journals Relationship of B7-H3 expression in tumor cells and tumor vasculature with FOXP3+ regulatory T cells in renal cell carcinoma

2019 ◽  
Vol Volume 11 ◽  
pp. 7021-7030 ◽  
Author(s):  
Kentaro Inamura ◽  
Gulanbar Amori ◽  
Takeshi Yuasa ◽  
Shinya Yamamoto ◽  
Junji Yonese ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Tumor Vasculature ◽  
Relationship Of

scholarly journals Tryptophan 2,3‐dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma

2021 ◽  
Author(s):  
Makoto Sumitomo ◽  
Kiyoshi Takahara ◽  
Kenji Zennami ◽  
Tomomi Nagakawa ◽  
Yasuhiro Maeda ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell

Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells

Tumor Biology ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 551-559 ◽  
Author(s):  
Minoru Kobayashi ◽  
Tatsuo Morita ◽  
Nicole A. L. Chun ◽  
Aya Matsui ◽  
Masafumi Takahashi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Metastatic Potential ◽  
Host Immunity ◽  
In Vivo Models ◽  
Metastatic Behavior

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

Diagnostic ability of four cell-free miRNA signatures pre- and post-nephrectomy concordantly found in the tumor and blood from patients with renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16577-e16577
Author(s):  
Matias Bustos ◽  
Rebecca Gross ◽  
Rebeka Dejenie ◽  
Ryu Suyeon ◽  
Negin Rahimzadeh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Incidental Finding ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Ability ◽  
Paired Samples ◽  
Tumor Tissues

e16577 Background: Renal cell carcinoma (RCC) has shown an increase in incidence based on continued incidental finding of these tumors by imaging. There is a need for reliable biomarkers like MicroRNAs (miRNA) that are released by the tumor cells and can be detected in assays using blood or urine samples. The first aim of the present pilot study is to determine the diagnostic ability of cell-free miRNA (cfmiR) biomarkers released by RCC tumor cells in urine and plasma samples. The secondary aim was to determine cfmiRs utility in monitoring RCC before and after radical or partial nephrectomy. Methods: We profiled tumor tissues (n = 11), pre-operative (pre-P n = 18; pre-U n = 17) and post-operative (post-P n = 18; post-U n = 17) plasma and urine paired samples from 18 RCC patients with a median follow-up of 18.4 months. As a control, we utilized plasma (n = 73) and urine (n = 16) samples taken from normal healthy donors (NHD). All specimens (n = 170) were processed and analyzed using HTG EdgeSeq miRNA whole transcriptome assay. All of the samples were normalized and DESeq2. Only miRNAs with a FC < -1.5 or > 1.5, FDR < 0.05, normalized counts > 30 were considered Results: We assessed urine, plasma, and tissue for 2083 miRNAs. The pre-U profiles from patients with RCC and NHD were compared to find differentially expressed (DE) cfmiRs. We found 182 cfmiRs DE in pre-U RCC, of which 106 were upregulated and 76 were downregulated. Similarly, we found 830 cfmiRs DE in the pre-P from RCC compared to NHD, of which 192 were upregulated and 638 were downregulated. We then searched for the top 100 miRNAs most frequently detected and identified in the tumor and in pre-P and pre-U samples. Forty miRNAs were consistently found and highly detected in all of the specimens. Of those 40 miRNAs, 33 cfmiRs were found DE in pre-P and 9 cfmiRs significantly decreased in post-P samples after surgery to the level values observed in the plasma from NHD. In the pre-P and pre-U samples from RCC patients, let-7a-5p, let-7b-5p, miR-23b-3p, and miR-30d-5p were found to be consistently upregulated compared to their respective controls. By using receiving operating characteristic (ROC) curves we assessed the area under the curve (AUC) of all the four cfmiRs in detecting RCC patients. The values of AUC for the four cfmiRs detected in pre-P ranged from 76.2-81% [sensitivity, 61.1-83.3%; specificity, 74-86.3%] and in pre-U samples ranged from 76.1-82.4% [sensitivity, 64.7-70.6%; specificity, 100%]. We observed that the four cfmiRs significantly decreased in the post-U samples from RCC patients after surgery to the level values observed in urine from NHD. Conclusions: Our results propose a four cfmiR signature as a potential diagnostic/monitoring urine biomarker that is also detectable in the plasma and tumor tissues from RRC. Further studies to validate these cfmiRNAs as biomarkers for RCC in blood and urine are ongoing.

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