scholarly journals The Concept of “Cancer Stem Cells” in the Context of Classic Carcinogenesis Hypotheses and Experimental Findings

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1308
Author(s):  
James E. Trosko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Operational Definition ◽  
Epigenetic Mechanisms ◽  
Gap Junctional Intercellular Communication ◽  
Cell Stage ◽  
Connexin Gene ◽  
Organ Specific

In this Commentary, the operational definition of cancer stem cells or cancer initiating cells includes the ability of certain cells, found in a heterogeneous mixture of cells within a tumor, which are able to sustain growth of that tumor. However, that concept of cancer stem cells does not resolve the age-old controversy of two opposing hypotheses of the origin of the cancer, namely the stem cell hypothesis versus the de-differentiation or re-programming hypothesis. Moreover, this cancer stem concept has to take into account classic experimental observations, techniques, and concepts, such as the multi-stage, multi-mechanism process of carcinogenesis; roles of mutagenic, cytotoxic and epigenetic mechanisms; the important differences between errors of DNA repair and errors of DNA replication in forming mutations; biomarkers of known characteristics of normal adult organ-specific stem cells and of cancer stem cells; and the characteristics of epigenetic mechanisms involved in the carcinogenic process. In addition, vague and misleading terms, such as carcinogens, immortal and normal cells have to be clarified in the context of current scientific facts. The ultimate integration of all of these historic factors to provide a current understanding of the origin and characteristics of a cancer stem cell, which is required for a rational strategy for prevention and therapy for cancer, does not follow a linear path. Lastly, it will be speculated that there exists evidence of two distinct types of cancer stem cells, one that has its origin in an organ-specific adult stem cell that is ‘initiated’ in the stem cell stage, expressing the Oct4A gene and not expressing any connexin gene or having functional gap junctional intercellular communication (GJIC). The other cancer stem cell is derived from a stem cell that is initiated early after the Oct4A gene is suppressed and the connexin gene is expressed, which starts early differentiation, but it is blocked from terminal differentiation.

scholarly journals Cancer Prevention and Therapy of Two Types of Gap Junctional Intercellular Communication–Deficient “Cancer Stem Cell”

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 87 ◽  
Author(s):  
James Trosko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Intercellular Communication ◽  
Adult Stem Cells ◽  
Gap Junctional Intercellular Communication ◽  
Organ Specific ◽  
Connexin Genes ◽  
Gap Junctional

Early observations showed a lack of growth control and terminal differentiation with a lack of gap junctional intercellular communication (GJIC). Subsequent observations showed that epigenetic tumor promoters and activated oncogenes, which block gap junction function, provide insights into the multi-stage, multi-mechanism carcinogenic process. With the isolation of embryonic induced pluri-potent stem cells and organ-specific adult stem cells, gap junctions were linked to early development. While tumors and tumor cell lines are a heterogeneous mixture of “cancer stem cells” and “cancer non-stem cells”, the cancer stem cells seem to be of two types, namely, they express (a) no connexin genes or (b) connexin genes, but do not have functional GJIC. These observations suggest that these “cancer stem cells” originate from normal adult stem cells or from the de-differentiation or re-programming of somatic differentiated cells. This “Concept Paper” provides a hypothesis that “cancer stem cells” either originate from (a) organ-specific adult stem cells before the expression of the connexin genes or (b) organ-specific adult stem cells that just express gap junction genes but that the connexin proteins are rendered dysfunctional by activated oncogenes. Therefore, cancer prevention and therapeutic strategies must account for these two different types of “cancer stem cell”.

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 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.

A tri-metallic palladium complex with breast cancer stem cell potency

2020 ◽  
Vol 49 (14) ◽  
pp. 4211-4215
Author(s):  
Arvin Eskandari ◽  
Arunangshu Kundu ◽  
Alice Johnson ◽  
Sanjib Karmakar ◽  
Sushobhan Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Palladium Complex ◽  
Breast Cancer Stem Cell ◽  
Metallic Palladium ◽  
Micromolar Range

A multi-nuclear, triangular-shaped palladium(ii) complex is shown to equipotently kill bulk cancer cells and cancer stem cells (CSCs) in the micromolar range.

scholarly journals Cancer Stem Cells and Epithelial Ovarian Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sheetal Dyall ◽  
Simon A. Gayther ◽  
Dimitra Dafou
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Epithelial Ovarian Cancer ◽  
Primary Tumour ◽  
Cellular Level ◽  
Small Population ◽  
Novel Target

The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs), or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

scholarly journals Quinoline based mono- and bis-(thio)carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

RSC Advances ◽  
2016 ◽  
Vol 6 (106) ◽  
pp. 104763-104781 ◽  
Author(s):  
Aleksandra Božić ◽  
Aleksandar Marinković ◽  
Snežana Bjelogrlić ◽  
Tamara R. Todorović ◽  
Ilija N. Cvijetić ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Antitumor Activity ◽  
Cancer Stem Cell ◽  
Cell Models ◽  
Target Profile ◽  
Apoptotic Activity ◽  
2D And 3D ◽  
Stem Cell Models

Study of antitumor activity of mono- and bis-quinoline based (thio)carbohydrazones on THP-1 and AsPC-1 cancer stem cells, revealed that thiocarbohydrazones had superior pro-apoptotic activity than carbohydrazones with multi-target profile activities.

scholarly journals The Role of Cancer Stem Cells in Breast Cancer Initiation and Progression: Potential Cancer Stem Cell‐Directed Therapies

2012 ◽  
Vol 17 (11) ◽  
pp. 1394-1401 ◽  
Author(s):  
Panagiota Economopoulou ◽  
Virginia G. Kaklamani ◽  
Kalliopi Siziopikou
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Initiation ◽  
Potential Cancer
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