scholarly journals Identification of Cancer Stem Cells in Dog Glioblastoma

2009 ◽  
Vol 46 (3) ◽  
pp. 391-406 ◽  
Author(s):  
G. Stoica ◽  
G. Lungu ◽  
H. Martini-STOICA ◽  
S. Waghela ◽  
J. Levine ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Glioblastoma Multiforme ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Self Renewal ◽  
Great Capacity ◽  
The Past ◽  
Proliferation And Differentiation ◽  
Tumor Clone

There is increasing evidence in some malignancies that the tumor clone is heterogeneous in regard to proliferation and differentiation. The cancer stem cell hypothesis implies that not all the cells in the tumor have the same capacity to proliferate and maintain the growth of the tumor. Only a relatively small fraction of cells in the tumor, termed cancer stem cells (CSCs), possess the ability to proliferate and self-renew extensively. In the past decade, several groups have reported the existence of a CSC population in different human brain tumors from both children and adults. We report here the identification of a CSC population from a Boxer dog with glioblastoma multiforme (GBM) that possesses a great capacity for proliferation, self-renewal, and differentiation. This cloned cell line is aneuploid, forms neurospheres in culture, possesses CSC markers, and reproduces the original dog GBM when inoculated into the nude mouse brain.

Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells

2019 ◽  
Vol 14 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Gabriele D. Bigoni-Ordóñez ◽  
Daniel Czarnowski ◽  
Tyler Parsons ◽  
Gerard J. Madlambayan ◽  
Luis G. Villa-Diaz
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
The Self ◽  
Self Renewal ◽  
Terminal Disease

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

scholarly journals Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Thahomina Khan ◽  
Horacio Cabral
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Self Renewal ◽  
Tumor Relapse ◽  
Intracellular Signaling Pathways ◽  
Abnormal Glycosylation

Cancer stem cell (CSCs) are deemed as one of the main reasons of tumor relapse due to their resistance to standard therapies. Numerous intracellular signaling pathways along with extracellular features are crucial in regulating CSCs properties, such as heterogeneity, plasticity and differentiation. Aberrant glycosylation of these cellular signaling pathways and markers of CSCs have been directly correlated with maintaining survival, self-renewal and extravasation properties. In this review, we highlight the importance of glycosylation in promoting stemness character of CSCs, and present strategies for targeting abnormal glycosylation to eliminate the resistant CSC population.

Therapeutic resistance and tumor-initiation: Molecular pathways involved in breast cancer stem cell self-renewal

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 528-528 ◽  
Author(s):  
J. C. Chang ◽  
X. Li ◽  
H. Wong ◽  
C. Creighton ◽  
S. G. Hilsenbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Residual Disease ◽  
Molecular Pathways ◽  
Stem Cell Markers ◽  
Tumor Initiation ◽  
Self Renewal

528 Background: Recent evidence supports the existance of a rare subpopulation of ‘cancer stem cells‘ (CSCs) which is chemoresistant and capable of self-renewal and tumor-initiation, resulting in relapse and metastases. We hypothesized that residual breast tumors after conventional chemotherapy (CTx) are enriched for CSCs bearing CD44+/CD24- markers, and show increased self-renewal as demonstrated by mammosphere (MS) forming assays. Molecular pathways like Notch, Wnt, and the polycomb family that regulate normal mammary self-renewal may be in aberrant in CSCs. Methods: Paired breast cancer biopsies from 35 patients were obtained before and after 12 weeks of neoadjuvant CTx (docetaxel 100 mg/m2 or Adriamycin/Cytoxan 60/600 mg/m2, 4 cycles, q3weeks), digested by collagenase, stained with CD24/CD44/lineage antibodies, and analyzed by flow cytometry. MS assays were performed to measure self-renewal ability. Gene expression, using the Affymetrix U133 GeneChip platform, of cancer cells bearing CD44+/CD24- markers vs. all other sorted cells, and between secondary cancer MS vs. the primary bulk invasive cancers were analyzed. Results: CD44+/CD24- cells increased from a median of 4.8% to 14.8% after CTx (p<0.005). Increased self-renewal was demonstrated by an increase in MS capacity after CTx (p=0.03), with a positive correlation between the number of CD44+/24- cells and MS assays (R=0.8, p<0.05). Common molecular pathways shared by CD44+/CD24- cells and MS show increased expression in normal self-renewal pathways - polycomb family (PCGF5), Notch (MAML2), FOXP1, and BBX. In addition, genes governing alternative splicing were increased, including a non-coding RNA (MALAT1) of unknown function, and RNA splicing factors (SFRS3, SFRS21P, SFRS4). Conclusions: Our results with an increase in cells bearing stem cell markers, and increased MS formation of residual tumors provide the first strong clinical evidence for the existance of therapy-resistant cancer stem cells. Post-transcriptional regulation may play a crucial role in modifying gene function involved in cancer stem cell self-renewal. Clinical trials targeting these newly identified pathways may eradicate residual disease and improved cure rates for many breast cancer patients. [Table: see text]

scholarly journals Resident Stem Cells and Renal Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Benedetta Bussolati ◽  
Alessia Brossa ◽  
Giovanni Camussi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Renal Carcinoma ◽  
Stem Cell Population ◽  
Self Renewal ◽  
Resident Stem Cells ◽  
Renal Cancer Stem Cells

According to the cancer stem cell hypothesis tumors are maintained by a cancer stem cell population which is able to initiate and maintain tumors. Tumor-initiating stem cells display stem or progenitor cell properties such as self-renewal and capacity to re-establish tumors that recapitulate the tumor of origin. In this paper, we discuss data relative to the presence of cancer stem cells in human renal carcinoma and their possible origin from normal resident stem cells. The cancer stem cells identified in human renal carcinomas are not derived from the normal CD133+progenitors of the kidney, but rather from a more undifferentiated population that retains a mesenchymal phenotype. This population is able to self-renewal, clonogenicity, and in vivo tumor initiation. Moreover, they retain pluripotent differentiation capability, as they can generate not only the epithelial component of the tumor, but also tumor endothelial cells. This suggests that renal cancer stem cells may contribute to the intratumor vasculogenesis.

scholarly journals Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model

2018 ◽  
Vol 19 (11) ◽  
pp. 3345 ◽  
Author(s):  
Md Alam ◽  
Ryota Takahashi ◽  
Said Afify ◽  
Aung Oo ◽  
Kazuki Kumon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Stop Codon ◽  
Site Directed Mutagenesis ◽  
Soluble Form ◽  
Dependent Manner ◽  
Self Renewal ◽  
Mesenchymal Transition

Cripto-1 is a glycophosphatidylinositol (GPI) anchored signaling protein of epidermal growth factor (EGF)-Cripto-1-FRL1-Cryptic (CFC) family and plays a significant role in the early developmental stages and in the different types of cancer cells, epithelial to mesenchymal transition and tumor angiogenesis. Previously, we have developed cancer stem cells (miPS-LLCcm) from mouse iPSCs by culturing them in the presence of conditioned medium of Lewis Lung Carcinoma (LLC) cells for four weeks. Nodal and Cripto-1 were confirmed to be expressed in miPS-LLCcm cells by quantitative reverse transcription PCR (rt-qPCR) implying that Cr-1 was required in maintaining stemness. To investigate the biological effect of adding exogenous soluble CR-1 to the cancer stem cells, we have prepared a C-terminally truncated soluble form of recombinant human CR-1 protein (rhsfCR-1), in which the GPI anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. rhsfCR-1 effectively suppressed the proliferation and sphere forming ability of miPS-LLCcm cells in a dose-dependent manner in the range of 0 to 5 µg/mL, due to the suppression of Nodal-Cripto-1/ALK4/Smad2 signaling pathway. Frequency of sphere-forming cells was dropped from 1/40 to 1/69 by rhsfCR-1 at 1 µg/mL. Moreover, rhsfCR-1 in the range of 0 to 1 µg/mL also limited the differentiation of miPS-LLCcm cells into vascular endothelial cells probably due to the suppression of self-renewal, which should reduce the number of cells with stemness property. As demonstrated by a soluble form of exogenous Cripto-1 in this study, the efficient blockade would be an attractive way to study Cripto-1 dependent cancer stem cell properties for therapeutic application.

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster

2017 ◽  
Vol 46 (38) ◽  
pp. 12785-12789 ◽  
Author(s):  
C. Lu ◽  
K. Laws ◽  
A. Eskandari ◽  
K. Suntharalingam
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Schiff Base ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Cyclooxygenase 2 ◽  
Oxygen Species

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties,1–4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency.

scholarly journals Understanding the Influence of Substrate When Growing Tumorspheres

2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Stem Cell Niche ◽  
Cell Number ◽  
Hard Substrate ◽  
Cell Niche

Abstract Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. A specific condition for the growth of the cancer stem cell number is also obtained.

scholarly journals NQO1 is Required for β-Lapachone-Mediated Downregulation of Breast-Cancer Stem-Cell Activity

2018 ◽  
Vol 19 (12) ◽  
pp. 3813 ◽  
Author(s):  
Dong Kim ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Breast Cancer Stem Cell ◽  
Cancer Development ◽  
Dependent Manner ◽  
Mammosphere Formation

Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. The β-lapachone (bL) compound is widely used to treat cancer development; however, its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast-cancer stem-cell (BCSC) marker-positive cells, MDA-MB-231. MDA-MB-231 cells, which are negative for reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase (NQO1) expression, were constructed to stably express NQO1 (NQO1 stable cells). The effect of bL on these cells was evaluated by wound healing and Transwell cell-culture chambers, ALDEFLUOR assay, and mammosphere formation assay. Here, we show that bL inhibited the proliferative ability of mammospheres derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. The bL treatment efficiently downregulated the expression level of BCSC markers cluster of differentiation 44 (CD44), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and discs large (DLG)-associated protein 5 (DLGAP5) that was recently identified as a stem-cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulated cell proliferation and migration activities. These results strongly suggest that bL could be a therapeutic agent for targeting breast-cancer stem-cells with proper NQO1 expression.

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