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Final Thoughts: Complexity and Controversy Surrounding the “Cancer Stem Cell” Paradigm

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Cancer Stem Cells in Solid Tumors

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

Many patients die of cancers that are metastatic at presentation, or relapse after treatment with curative intent. Cancers are known to contain heterogeneous populations of cells. The cancer stem cell (CSC) hypothesis posits the intriguing possibility that cancer cells are hierarchically organized, such that an identifiable subgroup of these cells may cause metastatic spread, treatment failure, and relapse. These “CSCs” should then become the focus of our research and treatment efforts. Although there is increasing evidence to support this hypothesis, it remains controversial due to increasing complexities in the data reported. We will discuss these maturing data under the framework of the scientific method itself; how we formulate and conceptualize the hypothesis, how we experimentally test the hypothesis, and how we analyze our experimental data. Whether tumor heterogeneity is ultimately determined to be hierarchical or stochastic, interrogating the CSC hypothesis will lead to novel mechanistic insights and improved outcomes for patients with cancer.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

AML:

Acute myeloid leukemia

BLAST:

Basic local alignment search tool

BRCA:

Breast cancer susceptibility gene

CD:

Cluster of differentiation

CSC:

Cancer stem cell

EHS:

Engelbreth-Holm-Swarm

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ESA:

Epithelial specific antigen

GM-CSF:

Granulocyte macrophage colony-stimulating factor

HGF:

Hepatocyte growth factor

IGH:

Immunoglobulin heavy chain

IL:

Interleukin

iPS:

Induced pluripotent stem cells

LIC:

Leukemia-initiating cell

NCBI:

National Center for Biotechnology Information

NGFR:

Nerve growth factor receptor

NK:

Natural killer

NOD/SCID:

Nonobese diabetic/severe combined immune deficiency

NSG:

NOD/SCID/IL2Rγ−/−

PDGFR:

Platelet-derived growth factor receptor

PECAM1:

Platelet endothelial cell adhesion molecule 1

SCF:

Stem cell factor

Shh:

Sonic hedgehog

TGF-β:

Transforming growth factor beta

TIC:

Tumor-initiating cells

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Acknowledgments

Thanks to Francis Ouellette for helpful advice. This research was funded in part by the Ontario Ministry of Health and Long Term Care. The views expressed do not necessarily reflect those of the OMOHLTC. CG is supported by a Royal Australasian College of Physicians CSL Fellowship and a National Health and Medical Research Council Overseas Postdoctoral Fellowship. LEA is supported by a new investigator award from the Ontario Institute for Cancer Research. RPH is supported by funds from the Terry Fox Foundation and the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Ontario Cancer Institute, Campbell Family Institute of Cancer Research, Toronto, ON, Canada

    Craig Gedye & Laurie Ailles

  2. Ontario Cancer Institute, Campbell Family Institute of Cancer Research, Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, ON, Canada

    Richard P. Hill

  3. Departments of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Laurie Ailles

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  1. Craig Gedye
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  2. Richard P. Hill
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  3. Laurie Ailles
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Correspondence to Laurie Ailles .

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  1. Dept. Oncology & Anatomy & Cell Biology, University of Western Ontario, Commissioners Road East 790, London, N6A 4L6, Ontario, Canada

    Alison L. Allan

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Gedye, C., Hill, R.P., Ailles, L. (2011). Final Thoughts: Complexity and Controversy Surrounding the “Cancer Stem Cell” Paradigm. In: Allan, A. (eds) Cancer Stem Cells in Solid Tumors. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-246-5_24

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