A 3D Cellular Automaton for Cell Differentiation in a Solid Tumor with Plasticity

2018 ◽  
Vol 13 (01) ◽  
pp. 19-28 ◽  
Author(s):  
David H. Margarit ◽  
Lilia Romanelli ◽  
Alejandro J. Fendrik
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Cellular Automaton ◽  
Solid Tumor ◽  
Spherical Symmetry ◽  
Differentiated Cells ◽  
Previous State

A model with spherical symmetry is proposed. We analyze the appropriate parameters of cell differentiation for different kinds of cells (Cancer Stem Cells (CSC) and Differentiated Cells (DC)). The plasticity (capacity to return from a DC to its previous state of CSC) is taken into account. Following this hypothesis, the dissemination of CSCs to another organ is analyzed. The location of the cells in the tumor and the plasticity range for possible metastasis is discussed.

scholarly journals Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Immune Cells ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Tumor Microenvironments

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.

scholarly journals Metabolic Targeting of Cancer Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Anna Mukha ◽  
Anna Dubrovska
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Clonal Evolution ◽  
Cancer Therapies ◽  
Intrinsic Resistance ◽  
Anti Cancer ◽  
Target Tumor Cell ◽  
High Degree ◽  
Metabolic Targeting

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor‐regenerating and tumor‐propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.

scholarly journals Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 28
Author(s):  
Gerardo Della Sala ◽  
Consiglia Pacelli ◽  
Francesca Agriesti ◽  
Ilaria Laurenzana ◽  
Francesco Tucci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Metabolic Flux ◽  
Confocal Imaging ◽  
Flux Analysis ◽  
Osteosarcoma Cell ◽  
Differentiated Cells ◽  
Cycle Arrest ◽  
Pathway Inhibition

Defining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. To this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. The results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. All together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy.

scholarly journals Unveiling metabolic vulnerability and plasticity of human osteosarcoma stem and differentiated cells to improve cancer therapy

2021 ◽  
Author(s):  
Gerardo Della Sala ◽  
Consiglia Pacelli ◽  
Francesca Agriesti ◽  
Ilaria Laurenzana ◽  
Francesco Tucci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Metabolic Flux ◽  
Confocal Imaging ◽  
Flux Analysis ◽  
Osteosarcoma Cell ◽  
Differentiated Cells ◽  
Cycle Arrest ◽  
Pathway Inhibition

Abstract BackgroundDefining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. MethodsTo this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. ResultsThe results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. ConclusionsAll together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy.

scholarly journals A Case of Identity: HOX Genes in Normal and Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 512 ◽  
Author(s):  
Smith ◽  
Zyoud ◽  
Allegrucci
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Hox Genes ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Hox Gene

Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment.

scholarly journals Correction: By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy

Oncotarget ◽  
2019 ◽  
Vol 10 (48) ◽  
pp. 5003-5004 ◽  
Author(s):  
Annalisa Petrelli ◽  
Rosachiara Carollo ◽  
Marilisa Cargnelutti ◽  
Flora Iovino ◽  
Maurizio Callari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Hormonal Therapy ◽  
Breast Cancer Stem Cells ◽  
Basal Like Breast Cancer

scholarly journals Phenotypic Heterogeneity of Breast Cancer Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Aurelio Lorico ◽  
Germana Rappa
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Radiation Treatment ◽  
Tumor Formation ◽  
Leukemic Cells ◽  
Leukemia Stem Cell ◽  
Differentiated Cells ◽  
Solid Malignancies ◽  
Undifferentiated Cells ◽  
Survival Signaling

Many types of tumors are organized in a hierarchy of heterogeneous cell populations, with only a small proportion of cancer stem cells (CSCs) capable of sustaining tumor formation and growth, giving rise to differentiated cells, which form the bulk of the tumor. Proof of the existence of CSC comes from clinical experience with germ-cell cancers, where the elimination of a subset of undifferentiated cells can cure patients (Horwich et al., 2006), and from the study of leukemic cells (Bonnet and Dick, 1997; Lapidot et al., 1994; and Yilmaz et al., 2006). The discovery of CSC in leukemias as well as in many solid malignancies, including breast carcinoma (Al-Hajj et al. 2003; Fang et al., 2005; Hemmati et al., 2003; Kim et al., 2005; Lawson et al., 2007; Li et al., 2007; Ricci-Vitiani et al., 2007; Singh et al., 2003; and Xin et al., 2005), has suggested a unifying CSC theory of cancer development. The reported general insensitivity of CSC to chemotherapy and radiation treatment (Bao et al., 2006) has suggested that current anticancer drugs, which inhibit bulk replicating cancer cells, may not effectively inhibit CSC. The clinical relevance of targeting CSC-associated genes is supported by several recent studies, including CD44 targeting for treatment of acute myeloid leukemia (Jin et al., 2006), CD24 targeting for treatment of colon and pancreatic cancer (Sagiv et al., 2008), and CD133 targeting for hepatocellular and gastric cancer (Smith et al., 2008). One promising approach is to target CSC survival signaling pathways, where leukemia stem cell research has already made some progress (Mikkola et al., 2010).

Role of E1B protein-dificient oncolytic virus in breast cancer stem cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22131-e22131
Author(s):  
F. Zhang ◽  
Y. Ma ◽  
Y. Xu ◽  
M. Huang ◽  
C. Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Oncolytic Adenovirus ◽  
Infected Group ◽  
Control Group ◽  
Breast Cancer Stem Cells ◽  
Differentiated Cells ◽  
Mcf 7

e22131 Background: Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44+CD24−/low population. Oncolytic adenoviruses enter cells through infection and can kill both proliferating and quiescent cells. We investigated the role of E1B protein- dificient oncolytic adenovirus in breast cancer stem cells. Methods: MCF-7 cells were infected by E1B protein-dificient oncolytic adenovirus as infected group (MOI=100) and cultured routinely as control group simultaneously. The proportion of CD44+CD24- cells was assessed by flow cytometry (FCM) in two groups respectively. Meanwhile, mammosphere culture was done in two groups' cells to observe the size and number of mammospheres, calculate the mammosphere- forming efficiency (MFE). The proportion of CD44+CD24- cells in two groups' mammospheres was assessed by FCM. Results: The percentages of CD24-,CD44+, CD44+CD24- in the infected gruop were 43.9%, 63.26%, 22.19%, respectively. While in the control group, the percentages were 6.74%, 88.30%, 2.30%. In the infected group, the time of mammosphere's formation was earlier, the volumes of mammospheres were bigger and the MFE was higher than the control group (1.26%:0.9%). In two mammospheres' groups, the proportion of CD44+CD24- cells in experiment group and control group was 38.08% and 23.35%, respectively. Conclusions: E1B protein-dificient oncolytic adenovirus can kill MCF-7 cells in short time, mainly breast cancer differentiated cells. It maybe promote the growth of the breast cancer stem cells. It maybe accelerate the speed of self-renewed and differentiation of the breast cancer stem cells. No significant financial relationships to disclose.

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