Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

Saroufim, Anthony; Messai, Yosra; Hasmim, Meriem; Rioux, Nancy; Iacovelli, Roberto; Verhoest, G.; Bensalah, Karim; Jj, Patard; Albiges, L.; Azzarone, Bruno; Escudier, Bernard; Chouaı̈b, Salem

doi:10.1038/bjc.2014.71

Cited by 49 publications

(45 citation statements)

References 27 publications

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“…Moreover, we demonstrate a strong and independent prognostic value of angiogenic patterns and also of the Ki67 tumour cell proliferation index on patients' OS from BM diagnosis. In line with our data, both Ki67 index and microvascularization were repeatedly described as prognostic factor in extracranial manifesta-tions of renal cell carcinoma [30][31][32][33][34]. Pending validation of our results in independent data sets, incorporation of these tissue-based parameters into prognostic scores (e.g.…”

Section: Discussionsupporting

confidence: 86%

Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases

Berghoff

Ilhan-Mutlu

Dinhof

et al. 2015

Neuropathology Appl Neurobio

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Section: Discussionsupporting

confidence: 86%

Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases

Berghoff

Ilhan-Mutlu

Dinhof

et al. 2015

Neuropathology Appl Neurobio

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“…CD105 + CSCs were able to differentiate into epithelial and endothelial cells and generate CD105 – cells. Additionally, immunohistochemical analysis of tumoural CD105 was found to correlate positively with nuclear grade and tumor stage, whereas endothelial expression correlated negatively with clinicopathological features . Thus, CD105 has been proposed as the main marker for CSC identification in RCC.…”

Section: Cancer Stem Cell Biomarkersmentioning

confidence: 97%

Biomarker discovery for renal cancer stem cells

Corrò

Moch

2018

The Journal of Pathology CR

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Characterised by high intra‐ and inter‐tumor heterogeneity, metastatic renal cell carcinoma (RCC) is resistant to chemo‐ and radiotherapy. Therefore, the development of new prognostic and diagnostic markers for RCC patients is needed. Cancer stem cells (CSCs) are a small population of neoplastic cells within a tumor which present characteristics reminiscent of normal stem cells. CSCs are characterised by unlimited cell division, maintenance of the stem cell pool (self‐renewal), and capability to give rise to all cell types within a tumor; and contribute to metastasis in vivo (tumourigenicity), treatment resistance and recurrence. So far, many studies have tried to establish unique biomarkers to identify CSC populations in RCC. At the same time, different approaches have been developed with the aim to isolate CSCs. Consequently, several markers were found to be specifically expressed in CSCs and cancer stem‐like cells derived from RCC such as CD105, ALDH1, OCT4, CD133, and CXCR4. However, the contribution of genetic and epigenetic mechanisms, and tumor microenvironment, to cellular plasticity have made the discovery of unique biomarkers a very difficult task. In fact, contrasting results regarding the applicability of such markers to the isolation of renal CSCs have been reported in the literature. Therefore, a better understanding of the mechanism underlying CSC may help dissecting tumor heterogeneity and drug treatment efficiency.

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“…CD105 (endoglin) is a member of the transforming growth factor (TGF-β1 and β3) receptor complex and modulates TGF-β signaling by influencing receptor cellular localization and cellular migration [26]. CD105 promotes angiogenesis, regulates cytoskeleton organization, and affects cell morphology and migration [27–29]. CD105+ cells may also promote tumor metastasis by circulating tumor cells [16, 30].…”

Section: Introductionmentioning

confidence: 99%

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

et al. 2016

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BackgroundRecent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells—stem cell-like cancer cells (SCLCCs)—which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells. The main goal of the project was to describe the gene-expression profile of stem cell-like cancer cells of primary tumor and metastatic origin.Materials and MethodsReal-time PCR analysis of stemness genes (Oct-4, Nanog and Ncam) and soft agar colony formation assay were conducted to check the stemness properties of renal cell carcinoma (RCC) cell lines. FACS analysis of CD105+ and CD133+ cells was performed on RCC cells. Isolated CD105+ cells were verified for expression of mesenchymal markers—CD24, CD146, CD90, CD73, CD44, CD11b, CD19, CD34, CD45, HLA-DR and alkaline phosphatase. Hanging drop assay was used to investigate CD105+ cell-cell cohesion. Analysis of free-floating 3D spheres formed by isolated CD105+ was verified, as spheres have been hypothesized to contain undifferentiated multipotent progenitor cells. Finally, CD105+ cells were sorted from primary (Caki-2) and metastatic (ACHN) renal cell cancer cell lines. Gene-expression profiling of sorted CD105+ cells was performed with Agilent’s human GE 4x44K v2 microarrays. Differentially expressed genes were further categorized into canonical pathways. Network analysis and downstream analysis were performed with Ingenuity Pathway Analysis.ResultsMetastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony-forming ability in comparison to primary RCC cell lines. Metastatic RCC cell lines harbor numerous CD105+ cell subpopulations and have higher expression of stemness genes (Oct-4 and Nanog). CD105+ cells adopt 3D grape-like floating structures under handing drop conditions. Sorted CD105+ cells are positive for human mesenchymal stem cell (MSC) markers CD90, CD73, CD44, CD146, and alkaline phosphatase activity, but not for CD24 and hematopoietic lineage markers CD34, CD11b, CD19, CD45, and HLA-DR. 1411 genes are commonly differentially expressed in CD105+ cells (both from primary [Caki-2] and metastatic RCC [ACHN] cells) in comparison to a healthy kidney epithelial cell line (ASE-5063). TGF-β, Wnt/β-catenine, epithelial-mesenchymal transition (EMT), Rap1 signaling, PI3K-Akt signaling, and Hippo signaling pathway are deregulated in CD105+ cells. TGFB1, ERBB2, and TNF are the most significant transcriptional regulators activated in these cells.ConclusionsAll together, RCC-CD105+ cells present stemlike properties. These stem cell-like cancer cells may represent a novel target for therapy. A unique gene-expression profile of CD105+ cells could be used as initia...

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Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

Cited by 49 publications

References 27 publications

Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases

Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases

Biomarker discovery for renal cancer stem cells

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

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