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PMID: 7516873 Published · ppublish English Journal Article Review

Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?

Environmental health perspectives ·Vol. 101 Suppl 5 ·1993-12-00 ·Pages 15-26

Sell S

Abstract

Given the fundamental principle that cancer must arise from a cell that has the potential to divide, two major nonexclusive hypotheses of the cellular origin of cancer are that malignancy arises a) from stem cells due to maturation arrest or b) from dedifferentiation of mature cells that retain the ability to proliferate. The role of stem cells in carcinogenesis is clearly demonstrated in teratocarcinomas. The malignant stem cells of teratocarcinomas are derived from normal multipotent stem cells and have the potential to differentiate into normal benign mature tissue. A widely studied model supporting dedifferentiation has been the putative origin of hepatocarcinomas from "premalignant" foci and nodules induced in the rat liver by chemicals. However, the dedifferentiation concept for hepatocarcinogenesis is challenged by more recent interpretations indicating that hepatocellular carcinoma arises from maturation arrest caused by aberrant differentiation of determined stem cells. Either hypothesis is supported by the cellular changes that occur in the rodent liver after different hepatocarcinogenic regimens. The formation of foci and nodules from altered hepatocytes supports dedifferentiation; the proliferation of small oval cells with the potential to differentiate into either biliary ducts or hepatocytes supports arrested maturation of determined stem cells. It is now postulated that foci and nodular change reflect adaptive changes to the toxic effects of carcinogens and not "preneoplastic" stages to cancer. The stem cell model predicts that genotoxic chemicals induce mutations in the determined stem cell which may be expressed in its progeny. Proliferation of initiated cells is induced by promoting events which also allow additional mutations to occur.

MeSH Terms
Animals Carcinogens/toxicity Cell Differentiation Cell Division Hepatitis B/complications Humans Liver/cytology Liver Neoplasms, Experimental/etiology,pathology Models, Biological Neoplasms/etiology,pathology Neoplastic Stem Cells/pathology Stem Cells/cytology alpha-Fetoproteins/metabolism
Chemicals
Carcinogens alpha-Fetoproteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Sell S
Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston 77225.
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Article Info
Journal
Environmental health perspectives
Abbr.
Environ Health Perspect
ISSN
0091-6765
DOI
10.1289/ehp.93101s515
Published
1993-12-00
Pages
15-26
Language
English
Region
United States
NLM ID
0330411
PMCID
PMC1519468
Subset
IM
External Links
PubMed source DOI: 10.1289/ehp.93101s515 PMC Full Text View journal details
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