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Cancer Stem Cells: Formidable Allies of Cancer

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Abstract

Cancer stem cells (CSC) represent the subpopulation of cells within a tumour showing two fundamental properties of stem cells – self-renewal (the ability to make more of their own kind) and differentiation (the ability to generate diverse cell types present within a tissue). The CSC hypothesis posits that CSCs play an important role in tumour initiation, maintenance and progression. Furthermore, owing to their intrinsic drug resistance, they remain refractory to currently used therapy, thereby contributing to tumour relapse. Thus, targeting or taming CSCs can lead to more effective cancer treatment in the coming decades. In this review, we will discuss about the origin of CSC hypothesis, evidence showing their existence, clinical relevance and translational significance.

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Acknowledgments

The authors thank Ipsa Jain, Mohini Lahiry and Saurav Kumar for useful discussions and critical inputs in writing this article. AR is currently a Wellcome Trust DBT India Alliance Senior Fellow. AR acknowledges funding from DBT to AR, and support from DBT-IISc partnership programme, DST-FIST, UGC to the Department of MRDG.

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  1. Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560065, India

    Neha Deshpande & Annapoorni Rangarajan

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  1. Neha Deshpande
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Correspondence to Annapoorni Rangarajan.

Glossary

Cancer stem cells (CSCs)

Are cancer cells that possess the abilities analogous to normal stem cells, specifically the ability to self-renew and to differentiate to give rise to the heterogeneous population within the tumour.

Cre recombinase and LoxP site

Cre-Lox technique is used to generate knock-in, knock-out or flipping of segments within genes. Cre recombinase is expressed conditionally within the cells where genetic modification is desired and it recognizes loxP sites placed around the desired gene to cause recombination. The orientation of the loxP site determines the outcome of the recombination event.

Differentiation

Is a cellular process by which cells commit to a particular fate, i.e. they commit to form a particular cell type within the organ having a distinct set of functions.

Epigenetics

Refers to the heritable changes in gene expression that does not involve changes to the DNA sequence; a change in phenotype without a change in the genotype. These changes generally occur at the level of chromatin organization.

Epithelial-mesenchymal transition (EMT)

Is a complex process by which epithelial cells lose their epithelial properties like cell-cell, cell-matrix adhesion, apico-basal polarity, etc. and acquire mesenchymal characteristics like migratory and invasive capabilities. The reverse process is called mesenchymal-epithelial transition (MET) by virtue of which mesenchymal cells acquire epithelial properties.

Fluorescence-activated cell sorting (FACS)

Is a flow cytometry technique that allows heterogeneous populations to be segregated based on the expression of cell surface markers that have been fluorescently labelled.

Invasion and metastasis cascade

Is a multi-step process by which epithelial cancer cells invade into the local surrounding, enter the vasculature, lodge at distant sites where they give rise to secondary/ metastatic tumours.

Mammosphere

3D spheroid structures formed when mammary tumour cells are subjected to suspension condition on long term culture (7–10 days).

Mutation

Is defined as a change in the nucleotide sequence of DNA, the genetic material in most organisms. Heritable mutations are called germline mutations whereas others which affect only the organism in which they occur are called somatic mutations.

NOD/SCID mouse

Non-obese diabetic SCID mouse; an immunodeficient mouse strain that lacks B, T lymphocytes as well as NK cells.

SCID mouse

Severe combined immunodeficiency mouse; an immunodeficient mouse strain that lacks B and T lymphocytes.

Self-renewal

Is the ability by which one stem cell can give rise to more cells of the same cell type.

Stem cells

Are undifferentiated cells within tissues that possess the ability to self-renew and to differentiate into other cell type of that tissue. They maintain tissue homeostasis.

Symmetric division

Produces two daughter cells having the same cellular fate. Asymmetric division produces two daughter cells with different cellular fates.

Tumorigenicity

Defines the ability of cells to seed/initiate new tumours. It is generally tested by subcutaneously/orthotopically injecting cells into immunocompromised mice and checking for tumour formation.

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Deshpande, N., Rangarajan, A. Cancer Stem Cells: Formidable Allies of Cancer. Indian J Surg Oncol 6, 400–414 (2015). https://doi.org/10.1007/s13193-015-0451-7

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