The Cancer Stem Cell Hypothesis: in Search of Definitions, Markers, and Relevance

Overview

Journal Lab Invest

Specialty Pathology

Date 2008 Apr 2

PMID 18379567

Citations 88

Authors

Michail Shipitsin

Kornelia Polyak

Affiliations

Soon will be listed here.

Abstract

Cancer is a disease of genes. Inherited or somatic alterations in genes are what make a normal cell ignore growth-controlling signals and form a tumor that eventually leads to the destruction of the organism. Based on accumulated knowledge on the genetic composition of cancer cells, the clonal evolution model of tumorigenesis was established, which explains multiple aspects of human disease and clinical observations. However, the recently popularized cancer stem cell hypothesis questions that all or most tumor cells can participate in tumor evolution and restricts this property to a subset of them defined as 'cancer stem cells' due to their stem cell-like characteristics. Enthusiasm surrounding this area of investigation and its presumed clinical implications led to a spurt of studies in various cancer types and model systems. Rigorous study design and critical data interpretation have to be employed to test the scientific and clinical relevance of the cancer stem cell hypothesis and its relationship to the clonal evolution model.

Citing Articles

ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3.

Lin I, Awamleh Z, Sinvhal M, Wan A, Bondhus L, Wei A BMC Med Genomics. 2024; 17(1):282.

PMID: 39614348 PMC: 11606099. DOI: 10.1186/s12920-024-02039-7.

Meta-Analysis of Prognostic Significance of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma.

Tripathi A, Singh M, Mishra P, Fatima N, Kumar V Asian Pac J Cancer Prev. 2024; 25(10):3597-3607.

PMID: 39471027 PMC: 11711375. DOI: 10.31557/APJCP.2024.25.10.3597.

Unraveling cancer progression pathways and phytochemical therapeutic strategies for its management.

Sharma V, Chaudhary A, Bawari S, Gupta S, Mishra R, Khan S Front Pharmacol. 2024; 15:1414790.

PMID: 39246660 PMC: 11377287. DOI: 10.3389/fphar.2024.1414790.

Cancer Stem Cells: Detection and Characterization from Solid Tumors.

Rehman A, Panda S, Tirino V, Del Vecchio V Methods Mol Biol. 2024; 2835:215-228.

PMID: 39105918 DOI: 10.1007/978-1-0716-3995-5_18.

Interactions between diet and gut microbiota in cancer.

Nakatsu G, Andreeva N, MacDonald M, Garrett W Nat Microbiol. 2024; 9(7):1644-1654.

PMID: 38907007 DOI: 10.1038/s41564-024-01736-4.

References

Polyak K, Hahn W . Roots and stems: stem cells in cancer. Nat Med. 2006; 12(3):296-300. DOI: 10.1038/nm1379. View

Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

Ramirez-Castillejo C, Sanchez-Sanchez F, Andreu-Agullo C, Ferron S, Aroca-Aguilar J, Sanchez P . Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci. 2006; 9(3):331-9. DOI: 10.1038/nn1657. View

Bonnet D, Dick J . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3(7):730-7. DOI: 10.1038/nm0797-730. View

Shipitsin M, Campbell L, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J . Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007; 11(3):259-73. DOI: 10.1016/j.ccr.2007.01.013. View

Prince M, Sivanandan R, Kaczorowski A, Wolf G, Kaplan M, Dalerba P . Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007; 104(3):973-8. PMC: 1783424. DOI: 10.1073/pnas.0610117104. View

Kern S, Shibata D . The fuzzy math of solid tumor stem cells: a perspective. Cancer Res. 2007; 67(19):8985-8. DOI: 10.1158/0008-5472.CAN-07-1971. View

Reya T, Morrison S, Clarke M, Weissman I . Stem cells, cancer, and cancer stem cells. Nature. 2001; 414(6859):105-11. DOI: 10.1038/35102167. View

OBrien C, Pollett A, Gallinger S, Dick J . A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2006; 445(7123):106-10. DOI: 10.1038/nature05372. View

10.

Liu R, Wang X, Chen G, Dalerba P, Gurney A, Hoey T . The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007; 356(3):217-26. DOI: 10.1056/NEJMoa063994. View

11.

Dick J . Complexity of the human acute myeloid leukemia stem cell compartment: implications for therapy. Biol Blood Marrow Transplant. 2005; 11(2 Suppl 2):9-11. DOI: 10.1016/j.bbmt.2004.11.007. View

12.

Yu J, Vodyanik M, Smuga-Otto K, Antosiewicz-Bourget J, Frane J, Tian S . Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318(5858):1917-20. DOI: 10.1126/science.1151526. View

13.

Campbell L, Polyak K . Breast tumor heterogeneity: cancer stem cells or clonal evolution?. Cell Cycle. 2007; 6(19):2332-8. DOI: 10.4161/cc.6.19.4914. View

14.

Zheng X, Shen G, Yang X, Liu W . Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res. 2007; 67(8):3691-7. DOI: 10.1158/0008-5472.CAN-06-3912. View

15.

Sakariassen P, Prestegarden L, Wang J, Skaftnesmo K, Mahesparan R, Molthoff C . Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci U S A. 2006; 103(44):16466-71. PMC: 1618812. DOI: 10.1073/pnas.0607668103. View

16.

Shmelkov S, St Clair R, Lyden D, Rafii S . AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005; 37(4):715-9. DOI: 10.1016/j.biocel.2004.08.010. View

17.

Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin N . Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006; 9(5):391-403. DOI: 10.1016/j.ccr.2006.03.030. View

18.

Jensen J, Parmar M . Strengths and limitations of the neurosphere culture system. Mol Neurobiol. 2007; 34(3):153-61. DOI: 10.1385/MN:34:3:153. View

19.

Singh S, Clarke I, Terasaki M, Bonn V, Hawkins C, Squire J . Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63(18):5821-8. View

20.

Dalerba P, Cho R, Clarke M . Cancer stem cells: models and concepts. Annu Rev Med. 2006; 58:267-84. DOI: 10.1146/annurev.med.58.062105.204854. View