Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology

Silván, Unai; Díez-Torre, Alejandro; Arluzea, Jon; Andrade, Ricardo; Silio, Margarita; Aréchaga, Juan

doi:10.1016/j.diff.2009.06.002

Cited by 73 publications

(62 citation statements)

References 101 publications

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“…Regarding TGCTs, in vitro experiments in which ES and EC cell lines were cultured under hypoxic conditions, revealed that low oxygenation promoted faster proliferation, independently of the presence of LIF in the culture medium. In addition, expression of vasculogenic factors and endothelial markers, such as Placentallike Growth Factor (PlGF) or VEGF-A, together with endothelial cell markers was as well observed under low oxygenation cultures of ES cell lines (Silván et al, 2009b).…”

Section: Vascularization and Hypoxiamentioning

confidence: 97%

“…Since tumors derived from b1-null ES cells contained significantly lower number of host derived stromal cells, it is likely that this integrin is related with the vasculogenic process from host-derived endothelial precursors. However, a second vasculogenic mechanism in which transplanted ES cells differentiate into endothelial cells is as well possible (Silván et al, 2009b), even in the a5-null tumors (Taverna and Hynes, 2001). In fact, the a5 subunit has been reported to participate in the remodelling of the embryonic vascular system in a process that might resemble TGCT vascularization.…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

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The spermatogonial stem cell niche in testicular germ cell tumors

Silván

Díez-Torre²,

Moreno³

et al. 2013

Int. J. Dev. Biol.

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Spermatogonial stem cells (SSCs) are pluripotent elements found in the adult seminiferous epithelium between Sertoli cells and a basal lamina which covers the multilayered external wall of peritubular myoid cells. The microenvironment of this pluripotent stem cell niche creates the complex and dynamic system that is necessary for the initiation of spermatogenesis, but this system also contains factors which can potentially collaborate in the progression of testicular germ cell tumors (TGCTs). In this review, we summarize our current knowledge about some important structural and molecular features related to the SSC niche, including growth factors, adhesion molecules, extracellular matrix, mechanical stress and vascularization. We discuss their possible collaborative effects on the generation and progression of TGCTs, which are a type of cancer representing the most frequent neoplasia among young men and whose incidence has grown very quickly during the past decades in North America and Europe. In this regard, a better understanding of the pluripotent stem cell niche where these malignancies arise will provide further insights into the origin of TGCTs and the mechanisms underlying their growth and invasion of adjacent and distant tissues.

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Section: Vascularization and Hypoxiamentioning

confidence: 97%

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

The spermatogonial stem cell niche in testicular germ cell tumors

Silván

Díez-Torre²,

Moreno³

et al. 2013

Int. J. Dev. Biol.

Self Cite

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“…After starting differentiation, the expression levels of some genes are determined at the levels of transcription and translation. In 1984, Schindler and Sherman reported the profile of protein and mRNA expression in murine EC cells, and the expression patterns of specific genes were explored during differentiation of EC cells (Scott et al, 1984;Silvan et al, 2009). Additionally, studies on proteins and carbohydrates have been performed to characterize the EC cells and their induced descendants (Amano et al, 2010;Andrews et al, 1984;Jemmerson et al, 1985).…”

Section: Early Data From Embryonic Carcinoma Cellsmentioning

confidence: 99%

Embryonic Stem Cells: Introducing Exogenous Regulators into Embryonic Stem Cells

Cheon¹

2011

Embryonic Stem Cells - Basic Biology to Bioengineering

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“…Hypoxia (low oxygen tension) is a selective insult for genomic alterations that lead to chemotherapeutic resistance observed in CSC populations (13). Therefore, we selected our candidate CSCs in MPM cell lines (H28, H2052 and MSTO211H) based on CSC expansion under hypoxic culture.…”

Section: Genetic Profile Of Mpm and Normal Mesothelial Cell Linesmentioning

confidence: 99%

“…Selection of these cells has been primarily based on expression of putative CSC markers which include: CD133, ABCG2, Bmi-1, OCT4 and uPAR. CSCs are more resistant to chemotherapy than the differentiated cells of the tumor (12), through their quiescence, ability to repair DNA and adaptation to hypoxic environments (13). Chemoresistance, is in part, mediated by multi-drug resistance ABC transporter proteins (including breast cancer resistant protein, BCRP/ABCG2), which actively, in an ATPdependent manner extrude a large variety of drugs and drug conjugates from cells (14,15).…”

Section: Introductionmentioning

confidence: 99%

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed

Schmid¹

2010

Int J Oncol

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Abstract. Malignant pleural mesothelioma (MPM) is a lethal cancer of the mesothelium with high chemotherapeutic resistance via unknown mechanisms. A prevailing hypothesis states that cancer stem cells (CSCs) persist in tumors causing relapse after chemotherapy, thus, rendering these cells as critical targets responsible for tumor resistance and recurrence. We selected candidate CSC markers based on expansion under hypoxic conditions, a hallmark for the selection of chemoresistant cells; and investigated the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in three MPM cell lines and normal mesothelial cells by quantitative RT-PCR. Furthermore, we evaluated the chemotherapeutic resistance associated with each CSC marker by determining the change in CSC marker-mRNA levels as an index of drugresistance following treatment with either cisplatin or pemetrexed. We demonstrate the expression of CSC markers: CD133, Bmi-1, uPAR and ABCG2 in both normal and MPM cell lines. Bmi-1 + , uPAR + and ABCG2 + cells show a distinct role in conferring chemoresistance to cisplatin and pemetrexed in the malignant setting. By contrast, these markers have no apparent participation in chemoresistance to drug treatments in normal mesothelial cells. Intriguingly, CD133 revealed chemoresistant properties in both normal mesothelial and malignant pleural mesothelioma cells. This study provides evidence of putative CSCs conferring drug-resistance to cisplatin and pemetrexed in MPM cell lines. Specific targeting of these drug-resistant cells, while considering the functional heterogeneity of the MPM subtypes, may contribute to more focused and effective chemotherapeutic regimens for malignant pleural mesothelioma.

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Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology

Cited by 73 publications

References 101 publications

The spermatogonial stem cell niche in testicular germ cell tumors

The spermatogonial stem cell niche in testicular germ cell tumors

Embryonic Stem Cells: Introducing Exogenous Regulators into Embryonic Stem Cells

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed

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