Spheres isolated from human glioblastoma possess cancer stem cell-like phenotype and promote tumor progression

2010 ◽  
Vol 68 ◽  
pp. e429
Author(s):  
Hisaaki Takahashi ◽  
Kana Kobayashi ◽  
Akihiro Inoue ◽  
Hironobu Harada ◽  
Hajime Yano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Human Glioblastoma

scholarly journals Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype

2018 ◽  
Vol 2018 ◽  
pp. 1-28 ◽  
Author(s):  
Su Yeon Lee ◽  
Min Kyung Ju ◽  
Hyun Min Jeon ◽  
Yig Ji Lee ◽  
Cho Hee Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Cell Phenotype ◽  
Mesenchymal Transition

Metastasis is a major obstacle to the efficient and successful treatment of cancer. Initiation of metastasis requires epithelial-mesenchymal transition (EMT) that is regulated by several transcription factors, including Snail and ZEB1/2. EMT is closely linked to the acquisition of cancer stem cell (CSC) properties and chemoresistance, which contribute to tumor malignancy. Tumor suppressor p53 inhibits EMT and metastasis by negatively regulating several EMT-inducing transcription factors and regulatory molecules; thus, its inhibition is crucial in EMT, invasion, metastasis, and stemness. Metabolic alterations are another hallmark of cancer. Most cancer cells are more dependent on glycolysis than on mitochondrial oxidative phosphorylation for their energy production, even in the presence of oxygen. Cancer cells enhance other oncogenic metabolic pathways, such as glutamine metabolism, pentose phosphate pathway, and the synthesis of fatty acids and cholesterol. Metabolic reprogramming in cancer is regulated by the activation of oncogenes or loss of tumor suppressors that contribute to tumor progression. Oncogenic metabolism has been recently linked closely with the induction of EMT or CSC phenotypes by the induction of several metabolic enzyme genes. In addition, several transcription factors and molecules involved in EMT or CSCs, including Snail, Dlx-2, HIF-1α, STAT3, TGF-β, Wnt, and Akt, regulate oncogenic metabolism. Moreover, p53 induces metabolic change by directly regulating several metabolic enzymes. The collective data indicate the importance of oncogenic metabolism in the regulation of EMT, cell invasion and metastasis, and adoption of the CSC phenotype, which all contribute to malignant transformation and tumor development. In this review, we highlight the oncogenic metabolism as a key regulator of EMT and CSC, which is related with tumor progression involving metastasis and chemoresistance. Targeting oncometabolism might be a promising strategy for the development of effective anticancer therapy.

Apigenin Inhibits Cancer Stem Cell-Like Phenotypes in Human Glioblastoma Cells via Suppression of c-Met Signaling

2016 ◽  
Vol 30 (11) ◽  
pp. 1833-1840 ◽  
Author(s):  
Boram Kim ◽  
Narae Jung ◽  
Sanghun Lee ◽  
Jae Kyung Sohng ◽  
Hye Jin Jung
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cells

scholarly journals A2B5 Cells from Human Glioblastoma have Cancer Stem Cell Properties

2010 ◽  
Vol 20 (1) ◽  
pp. 211-221 ◽  
Author(s):  
Aurélie Tchoghandjian ◽  
Nathalie Baeza ◽  
Carole Colin ◽  
Myriam Cayre ◽  
Philippe Metellus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Human Glioblastoma

scholarly journals The C-X-C Motif Chemokine Ligand 1 Sustains Breast Cancer Stem Cell Self-Renewal and Promotes Tumor Progression and Immune Escape Programs

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefania Livia Ciummo ◽  
Luigi D’Antonio ◽  
Carlo Sorrentino ◽  
Cristiano Fieni ◽  
Paola Lanuti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Stem Cell ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Mammosphere Formation

Breast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, including SPP1/OPN, ACKR3/CXCR7, TLR4, TNFSF10/TRAIL and CCL18 and, to a lesser extent, immunostimulatory cytokines, including IL15, while it downregulates CCL2, CCL28, and CXCR4. CXCL1 downregulates TWIST2 and SNAI2, while it boosts TWIST1 expression in association with the loss of E-Cadherin, ultimately promoting BCSC epithelial-mesenchymal transition. Bioinformatic analyses of transcriptional data obtained from BC samples of 1,084 patients, reveals that CXCL1 expressing BCs mostly belong to the Triple-Negative (TN) subtype, and that BC expression of CXCL1 strongly correlates with that of pro-angiogenic and cancer promoting genes, such as CXCL2-3-5-6, FGFBP1, BCL11A, PI3, B3GNT5, BBOX1, and PTX3, suggesting that the CXCL1 signaling cascade is part of a broader tumor-promoting signaling network. Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC.

scholarly journals Toward understanding cancer stem cell heterogeneity in the tumor microenvironment

2018 ◽  
Vol 116 (1) ◽  
pp. 148-157 ◽  
Author(s):  
Federico Bocci ◽  
Larisa Gearhart-Serna ◽  
Marcelo Boareto ◽  
Mariana Ribeiro ◽  
Eshel Ben-Jacob ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Spatiotemporal Dynamics ◽  
Spatial Proximity ◽  
Mesenchymal Transition

The epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) formation are two paramount processes driving tumor progression, therapy resistance, and cancer metastasis. Recent experiments show that cells with varying EMT and CSC phenotypes are spatially segregated in the primary tumor. The underlying mechanisms generating such spatiotemporal dynamics in the tumor microenvironment, however, remain largely unexplored. Here, we show through a mechanism-based dynamical model that the diffusion of EMT-inducing signals such as TGF-β, together with noncell autonomous control of EMT and CSC decision making via the Notch signaling pathway, can explain experimentally observed disparate localization of subsets of CSCs with varying EMT phenotypes in the tumor. Our simulations show that the more mesenchymal CSCs lie at the invasive edge, while the hybrid epithelial/mesenchymal (E/M) CSCs reside in the tumor interior. Further, motivated by the role of Notch-Jagged signaling in mediating EMT and stemness, we investigated the microenvironmental factors that promote Notch-Jagged signaling. We show that many inflammatory cytokines such as IL-6 that can promote Notch-Jagged signaling can (i) stabilize a hybrid E/M phenotype, (ii) increase the likelihood of spatial proximity of hybrid E/M cells, and (iii) expand the fraction of CSCs. To validate the predicted connection between Notch-Jagged signaling and stemness, we knocked down JAG1 in hybrid E/M SUM149 human breast cancer cells in vitro. JAG1 knockdown significantly restricted tumor organoid formation, confirming the key role that Notch-Jagged signaling can play in tumor progression. Together, our integrated computational–experimental framework reveals the underlying principles of spatiotemporal dynamics of EMT and CSCs.

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