Stem cell dynamics and pretumor progression in the intestinal tract.
Colorectal carcinogenesis is a process that follows a stepwise cascade that goes from the normal to an invisible pretumor stage ultimately leading to grossly visible tumor progression. During pretumor progression, an increasing accumulation of genetic alterations occurs, by definition without visible manifestations. It is generally thought that stem cells in the crypt base are responsible for this initiation of colorectal cancer progression because they are the origin of the differentiated epithelial cells that occupy the crypt. Furthermore, they are characterized by a long life span that enables them to acquire these cumulative mutations. Recent studies visualized the dynamics of stem cells both in vitro and in vivo. Translating this work into clinical applications will contribute to the evaluation of patients' predisposition for colorectal carcinogenesis and may help in the design of preventive measures for high-risk groups. In this review, we outline the progress made in the research into tracing stem cell dynamics. Further, we highlight the importance and potential clinical value of tracing stem cell dynamics in pretumor progression.
Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands.
Huiying
H
Ma
Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands.
Folkert H M
FH
Morsink
Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands. g.j.a.offerhaus@umcutrecht.nl.
George Johan Arnold
GJ
Offerhaus
Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands.
Wendy W J
WW
de Leng
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*
Colorectal cancer; Dynamics; Pretumor progression; Stem cell; Trace