Endoglin Is Essential for the Maintenance of Self-Renewal and Chemoresistance in Renal Cancer Stem Cells

Hu, Junhui; Guan, Wei; Liu, Peijun; Dai, Jing; Tang, Kun; Xiao, Heng; Qian, Yuan; Sharrow, Allison C.; Ye, Zhangqun; Wu, Lily; Xu, Hua

doi:10.1016/j.stemcr.2017.07.009

Cited by 47 publications

(53 citation statements)

References 59 publications

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“…Due to high expression of the CD105 marker, also in our previous study (4%) 12 Caki-1 cell line was used in the present study. As CD105−expressing subpopulation in human RCC xenografts from patient (nephrectomy) samples was shown to possess high capability of self-renewal and ability to form spheres in cell culture in vitro in complement to tumors in mice 28 it remains interesting that CD105− cells also give rise to tumors in our study. It is known that TGFβ pathway activation promote RCC 3D sphere formation and CD105 expression is up-regulated in stem-promoting conditions 33 .…”

Section: Discussionmentioning

confidence: 85%

“…High CD105 mRNA expression was previously associated with RCC metastases and high tumor stage 29 . In RCC cell lines CD105 www.nature.com/scientificreports www.nature.com/scientificreports/ was reported by us to be highly expressed in metastatic Caki-1 cell line before 12 , as well as by other groups 28 . Moreover, detection of CD105 marker in peripheral blood is considered to be effective tool to evaluate the early metastasis in RCC, especially in a cancer stem cell -positive conditions 30 .…”

Section: Discussionmentioning

confidence: 89%

“…present in most of RCC cell lines (SMKT-R3, Caki-2, 786-O, 769-P, RCC-6, Caki-1, ACHN and that CD105+ cells express also alkaline phosphatase (AP) 12 . The exact size of CD105+ cells subpopulation within the cell lines range from 0.03% (786-0), 0.06% (ACHN) to 2.17% (OS-RC2), but in as much as 90.93% (Caki-1) to 93.9% (SN12PM6) cells may be positive 28 . In RCC the association of CD105 with different disease stages is complex, but CD105 may through translation initiation of targeted genes promote RCC progression 29 .…”

Section: Discussionmentioning

confidence: 99%

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Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Fiedorowicz

Khan

Strzemecki

et al. 2020

Sci Rep

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clear cell renal cell carcinoma (ccRcc) is the most common kidney cancer. prognosis for ccRcc is generally poor since it is largely resistant to chemo-and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/ tics isolated from established Rcc cell lines-basic ccRcc research model-has never been investigated in vivo. CD105+, CD105−, CD44+ and CD44− as well as CD44−/CD105− CD44+/CD105+ and CD44−/ CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into noD SciD mice and tumor growth was monitored with MRi and pet/ct. tumor growth was observed after implantation of CD105+, CD44+, CD44−, CD44−/CD105+ and CD44−/CD105− but not CD105− or CD44+/CD105+. Implantation of CD44−/CD105− cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44− tumors expresses Nanog and Oct-4, while CD44− tumors additionally expressed endothelial cell marker-CD31. Renal cell carcinoma (RCC), is the 10th malignancy worldwide and the most frequent type of kidney cancer in adults. Each year in Europe approximately 88 400 patients are diagnosed with RCC; the incidence and mortality of RCC are rising at a rate of 2-3% per decade, therefore novel therapies directed against RCC are needed. At the same time despite advancements in diagnostic techniques, up to 30% of newly diagnosed patients already present with metastases, and a large portion of patients that undergo surgical treatment experience the RCC recurrence, therefore drugs targeted against metastasis initiating cells would be of great interest in the future 1,2. Cancer stem cells (CSCs) are characterized by the potential to self-renew, high tumorigenicity in nude mice and the ability to efficiently reconstitute all tumor subpopulations and primary tumor phenotype 3-5. CSCs are also responsible not only for cancer development, but also for disease recurrence, progression and metastatic spread, together with cancer aggressiveness, including treatment resistance such as chemo/radiotherapy, and targeted treatment 6,7 , therefore basic research with careful model selection to understand their biology is mandatory to define novel potential therapeutic targets for all RCC subtypes 8,9 .

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Fiedorowicz

Khan

Strzemecki

et al. 2020

Sci Rep

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“…Endoglin (CD105) is a cell membrane glycoprotein overexpressed on proliferating endothelial cells that binds several factors of the TGF-β superfamily, suggesting that activation of this pathway may be responsible for tumor VEGF-independency [46]. In 1995, CD105 was described as a receptor overexpressed in tumor vasculature [47] and, more recently, it has been shown that high CD105 expression on vessels is correlated with poor prognosis in many solid tumors, such as kidney [48], prostate [49], and ovarian cancer [50]. CD105 was also described as a marker of CSC in renal cell carcinoma [16].…”

Section: Alternative Anti-angiogenic Antibodiesmentioning

confidence: 99%

Alternative Strategies to Inhibit Tumor Vascularization

Brossa

Buono

Fallo

et al. 2019

IJMS

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Endothelial cells present in tumors show different origin, phenotype, and genotype with respect to the normal counterpart. Various mechanisms of intra-tumor vasculogenesis sustain the complexity of tumor vasculature, which can be further modified by signals deriving from the tumor microenvironment. As a result, resistance to anti-VEGF therapy and activation of compensatory pathways remain a challenge in the treatment of cancer patients, revealing the need to explore alternative strategies to the classical anti-angiogenic drugs. In this review, we will describe some alternative strategies to inhibit tumor vascularization, including targeting of antigens and signaling pathways overexpressed by tumor endothelial cells, the development of endothelial vaccinations, and the use of extracellular vesicles. In addition, anti-angiogenic drugs with normalizing effects on tumor vessels will be discussed. Finally, we will present the concept of endothelial demesenchymalization as an alternative approach to restore normal endothelial cell phenotype.

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“…Consequently, specific markers such as CD105, ALDH1, CD44, CD133, and CXCR4 have been found in RCC‐derived cancer stem‐like cells . However, a single marker cannot be used for identifying all the CSCs, and therefore, we need to find an appropriate method to discover novel biomarkers and reveal the heterogeneity of CSCs. This can help in clarifying the role of CSCs in the occurrence, development, recurrence, metastasis, and multidrug resistance of renal tumors and can enable more personalized treatment strategies to establish novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

High‐dimensional single‐cell proteomics analysis reveals the landscape of immune cells and stem‐like cells in renal tumors

Zhao

et al. 2019

Clinical Laboratory Analysis

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3 Guangxi key laboratory for genomic and personalized medicine, Guangxi collaborative innovation center for genomic and personalized medicine, Abstract Background: Renal tumors are highly heterogeneous, and identification of tumor heterogeneity is an urgent clinical need for effective treatment. Mass cytometry (MC) can be used to perform high-dimensional single-cell proteomics analysis of heterogeneous samples via cytometry by time-of-flight (CyTOF), in order to achieve more accurate observation and classification of phenotypes within a cell population. This study aimed to develop a high-dimensional MC method for the detection and analysis of heterogeneity in renal tumors. Materials and Methods: We collected tissue samples from 8 patients with different types of renal tumors. Single-cell suspensions were prepared and stained using a panel of 28 immune cell-centric antibodies and a panel of 21 stem-like cell-centric antibodies. The stained cells were detected using CyTOF. Result: Renal tumors were divided into 25 immune cell subsets (4 CD4+ T cells, 7 CD8+ T cells, 1 B cells, 8 macrophages, 1 dendritic cells, 2 natural killer (NK) cells, 1 granulocyte, and 1 other subset) and 7 stem-like cells subsets (based on positivity of vimentin, CD326, CD34, CD90, CD13, CD44, and CD47). Different types of renal tumors have different cell subsets with significantly different characteristics. Conclusion: High-dimensional single-cell proteomics analysis using MC aids in the discovery and analysis of renal tumors heterogeneity. Additionally, it can be used to accurately classify the immune cell population and analyze the expression of stem cell-related markers in renal tumors. Our findings provide a valuable resource for deciphering tumor heterogeneity and might improve the clinical management of patients with renal tumors. K E Y W O R D S cancer stem cells, mass cytometry, renal tumors, tumor heterogeneity, tumor microenvironment How to cite this article: Li Z, Hu J, Qin Z, et al. Highdimensional single-cell proteomics analysis reveals the landscape of immune cells and stem-like cells in renal tumors. J Clin Lab Anal. 2020;34:e23155. https ://doi.

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Endoglin Is Essential for the Maintenance of Self-Renewal and Chemoresistance in Renal Cancer Stem Cells

Cited by 47 publications

References 59 publications

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Alternative Strategies to Inhibit Tumor Vascularization

High‐dimensional single‐cell proteomics analysis reveals the landscape of immune cells and stem‐like cells in renal tumors

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