The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis

Myszczyszyn, Adam; Rutkowski, Piotr; Matak, Damian; Szymanski, Lukasz; Lian, Fei; Kornakiewicz, Anna; Bartnik, Ewa; Kukwa, Wojciech; Kieda, Claudine; Szczylik, Cezary

doi:10.1007/s12015-015-9611-y

Cited by 67 publications

(58 citation statements)

References 265 publications

(458 reference statements)

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“…Cancer cell movement in the wound healing assay corresponds to the cell’s ability to exit a primary tumor, to penetrate into blood vessels, and to finally spread in vivo. In many cancer types, it has been proven that internal tumor hypoxia induces cancer migration potential both in vivo [72] and in vitro [73, 74], although our results show the opposite. Regardless of the CD105 or CD133 level, all analyzed cancer cell lines showed reduced migration potential in hypoxia.…”

Section: Discussioncontrasting

confidence: 82%

Functional significance of CD105-positive cells in papillary renal cell carcinoma

et al. 2017

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BackgroundCD105 was postulated as a renal cell carcinoma (RCC) stem cell marker, and CD133 as a putative RCC progenitor. Hypoxia, a natural microenvironment that prevails in tumors, was also incorporated into the study, especially in terms of the promotion of hypothetical stem-like cell properties.MethodsWithin this study, we verify the existence of CD105+ and CD133+ populations in selected papillary subtype RCC (pRCC) cell lines. Both populations were analyzed for correlation with stem-like cell properties, such as stemness gene expression, and sphere and colony formation. For the preliminary analysis, several RCC cell lines were chosen (786-O, SMKT-R2, Caki-2, 796-P, ACHN, RCC6) and the control was human kidney cancer stem cells (HKCSC) and renal cells of embryonic origin (ASE-5063). Four cell lines were chosen for further investigation: Caki-2 (one of the highest numbers of CD105+ cells; primary origin), ACHN (a low number of CD105+ cells; metastatic origin), HKCSC (putative positive control), and ASE-5063 (additional control).ResultsIn 769-P and RCC6, we could not detect a CD105+ population. Hypoxia variously affects pRCC cell growth, and mainly diminishes the stem-like properties of cells. Furthermore, we could not observe the correlation of CD105 and/or CD133 expression with the enhancement of stem-like properties.ConclusionsBased on this analysis, CD105/CD133 cannot be validated as cancer stem cell markers of pRCC cell lines.

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“…Another possible explanation is that the tumor biology changes beyond a certain mass, just as tumors in general cannot grow beyond a critical small size without neovascularization. A variant of this explanation is that at the center of expanding tumors are hypo-oxygenated cells that acquire more aggressive tumor traits [34,35,36]. …”

Section: Discussionmentioning

confidence: 99%

Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels

Carr

Guerra²

2016

Oncology

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Background: Hepatocellular carcinoma (HCC) is known to metastasize. However, there are few reports on patients with metastasis at the time of HCC diagnosis. Aims: To evaluate the incidence and characteristics of extrahepatic metastasis patients presenting at baseline with noncurable, advanced HCC. Results: The total HCC cohort was initially dichotomized into 2 subcohorts, with (n = 214) and without (n = 719) extrahepatic metastasis (‘metastasis'), and patient baseline characteristics were compared. The main findings for patients with metastasis (22.9% of total cohort) compared with other, nonmetastatic patients were: more advanced tumors, as judged by larger tumor diameters, more tumor multifocality and percent with portal vein thrombosis, higher blood α-fetoprotein and des γ-carboxy prothrombin levels and alkaline phosphatase (ALKP), but not bilirubin levels, and a lower incidence of cirrhosis. There was a strong correlation between increases in tumor size and percent of patients with metastasis. A subset of patients with larger tumors was identified with low blood ALKP levels and better survival. Survival in the total metastasis cohort was lower than in the non-metastasis cohort, as expected, but only in patients with smaller tumors. In patients with larger tumors, survival with or without metastasis was similar and poor. Conclusions: There was a lower incidence of cirrhosis in HCC patients with metastasis, and they had larger and more aggressive primary tumors. Patients with smaller, but not larger, tumors and metastasis had worse prognosis than patients without metastasis. A distinct subset of metastatic patients was identified that had better prognosis and low ALKP levels.

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“…CD133 + cancer cells were able to form spheres, gave rise to tumors in vivo and exhibited chemoresistance properties in colorectal carcinoma (CRC), HCC, lung cancer, glioblastoma, pancreatic cancer, and ovarian cancer. On the contrary, sorted CD133 + cells from RCC patients did not show tumourigenic capability in vivo although they expressed stem cell markers such as CD44, CD29, Vimentin, and Pax2 . When co‐transplanted with renal carcinoma cells, CD133 + progenitors significantly enhanced tumor development and growth.…”

Section: Cancer Stem Cell Biomarkersmentioning

confidence: 95%

“…These cells also expressed mesenchymal markers CD44, CD90, CD29, CD73, and Vimentin; embryonic stem cell markers Oct3/4, Nanog and Nestin, and the embryonic renal marker Pax2 [48]. However, they did not express CD133, also known as human tubular progenitor cell marker [58]. CD105 1 CSCs were able to differentiate into epithelial and endothelial cells and generate CD105cells.…”

Section: Cd105mentioning

confidence: 98%

Biomarker discovery for renal cancer stem cells

Corrò

Moch

2018

J Path: Clin Res

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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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“…36117-44). The role of CSCs in RCC has been reviewed elsewhere [94], as they are potential treatment targets [95]. They are putatively tumor-initiating cells that promote disease development and progression and may be distinguished using different approaches.…”

Section: Introductionmentioning

confidence: 99%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Therapeutics against renal cell cancer (RCC) are also screened with the use of cell lines. Multiple RCC in vitro cultures are available, allowing in vivo heterogeneity in the laboratory, but at the same time, these can be a source of errors. In this review, we tried to sum up the data on the RCC cell lines used currently. An increasing amount of data on RCC shed new light on the molecular background of the disease; however, it revealed how much still needs to be done. As new types of RCC are being distinguished, novel cell lines and the re-exploration of old ones seems to be indispensable to create effective in vitro tools for drug screening and more.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0565-8) contains supplementary material, which is available to authorized users.

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The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis

Cited by 67 publications

References 265 publications

Functional significance of CD105-positive cells in papillary renal cell carcinoma

Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels

Biomarker discovery for renal cancer stem cells

Choosing the right cell line for renal cell cancer research

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