scholarly journals Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Pedro M. Aponte ◽  
Andrés Caicedo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Adult Stem Cells ◽  
Future Research ◽  
Differentiated Cells ◽  
Essential Components ◽  
A Cell ◽  
Cell Niche

Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

scholarly journals Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nathan Moore ◽  
Stephen Lyle
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Cell Cycle Regulators ◽  
Slow Cycling ◽  
Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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 Maintenance of Adult Stem Cells: Role of the Stem Cell Niche

2011 ◽  
pp. 35-55 ◽  
Author(s):  
Yoshiko Matsumoto ◽  
Hiroko Iwasaki ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Cell Niche

scholarly journals Regulation of Prostatic Stem Cells by Stromal Niche in Health and Disease

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4303-4306 ◽  
Author(s):  
Gail P. Risbridger ◽  
Renea A. Taylor
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Tumor Stroma ◽  
Stem Cell Differentiation ◽  
Stem Cell Regulation ◽  
Isolation And Characterization ◽  
Tissue Recombination ◽  
Cell Niche

The isolation and characterization of prostatic stem cells has received significant attention in the last few years based on the belief that aberrant regulation of adult stem cells leads to prostate disease including cancer. The nature of the perturbations in stem cell regulation remains largely unknown. Although adult stem cells are can be governed by autonomous regulatory mechanisms, the stromal niche environment also provides essential cues to direct directing differentiation decisions and can lead to aberrant proliferation and/or differentiation. Elegant tissue recombination experiments, pioneered by Gerald Cunha and colleagues, provided evidence that quiescent epithelial tissues containing adult stem cells were capable of altered differentiation in response to inductive and instructive mesenchyme. In more recent times, it has been demonstrated that embryonic mesenchyme is sufficiently powerful to direct the differentiation of embryonic stem cells into mature prostate or bladder. In addition, prostatic tumor stroma provides another unique niche or microenvironment for stem cell differentiation that is distinct to normal stroma. This review highlights the importance of the appropriate selection of the stromal cell niche for tissue regeneration and implies plasticity of adult stem cells that is dictated by the tissue microenvironment.

scholarly journals Heterogeneity of Cancer Stem Cells: Rationale for Targeting the Stem Cell Niche

2016 ◽  
Vol 1866 (2) ◽  
pp. 276-289 ◽  
Author(s):  
Maximilian Boesch ◽  
Sieghart Sopper ◽  
Alain G. Zeimet ◽  
Daniel Reimer ◽  
Guenther Gastl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Stem Cell Niche ◽  
Cell Niche

The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment

Tumor Biology ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 3945-3951 ◽  
Author(s):  
Jun Ye ◽  
Dang Wu ◽  
Pin Wu ◽  
Zhigang Chen ◽  
Jian Huang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cross Talk ◽  
Stem Cell Niche ◽  
Cell Niche

Mechanical Regulation of Stem Cell Proliferation and Fate Decisions by their Differentiated Daughters

2020 ◽  
Author(s):  
Wenxiu Ning ◽  
Andrew Muroyama ◽  
Hua Li ◽  
Terry Lechler
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Epidermal Keratinocytes ◽  
Stem Cell Proliferation ◽  
Differentiated Cells ◽  
Basal Progenitor ◽  
Cell Niche ◽  
And Migration ◽  
Tissue Tension

AbstractBasal stem cells fuel development, homeostasis, and regeneration of the epidermis. The proliferation and fate decisions of these cells are highly regulated by their microenvironment, including the basement membrane and underlying mesenchymal cells. Basal progenitors give rise to differentiated progeny that serve an essential role in generating the epidermal barrier. Here, we present data that differentiated progeny also regulate the proliferation, differentiation, and migration of basal progenitor cells. Using two distinct mouse lines, we found that increasing contractility of differentiated cells resulted in non-cell autonomous hyperproliferation of stem cells and prevented their commitment to a hair follicle lineage. These phenotypes were rescued by pharmacological inhibitors of contractility. Live-imaging revealed that increasing the contractility of differentiated cells resulted in stabilization of adherens junctions and impaired movement of basal progenitors during hair placode morphogenesis, as well as a defect in migration of melanoblasts. These data suggest that intra-tissue tension regulates stem cell proliferation, fate decisions and migration, similar to the known roles of extracellular matrix rigidity. Additionally, this work demonstrates that differentiated epidermal keratinocytes are a component of the stem cell niche that regulates development and homeostasis of the skin.

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 mRNA-Expression of ERα, ERβ, and PR in Clonal Stem Cell Cultures Obtained from Human Endometrial Biopsies

2011 ◽  
Vol 11 ◽  
pp. 1762-1769 ◽  
Author(s):  
A. N. Schüring ◽  
J. Braun ◽  
S. Wüllner ◽  
L. Kiesel ◽  
M. Götte
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Direct Stimulation ◽  
Regenerative Capacity ◽  
Endometrial Stem Cells ◽  
Proliferation And Differentiation ◽  
Clonal Cultures ◽  
Cell Niche

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies.Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβand PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression.Results. Expression of ERαand ERβwas downregulated by 64% and 89%, respectively ( and ). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern.Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERαand ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.

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