Amplification and invasiveness of epithelial progenitors during gastric carcinogenesis in trefoil factor 1 knockout mice.
OBJECTIVE
It is not known whether or not epithelial progenitors of the pyloric antrum are involved in gastric carcinogenesis. Normally, these progenitors give rise to two main cell lineages: pit and gland mucous cells. This study was designed to examine the changes that occur in pyloric antral mucous cell lineages and their progenitors during development of gastric adenoma and carcinoma in trefoil factor 1 (TFF1) knockout mice.


METHODS
Pyloric antral mucosal tissues of TFF1 knockout mice at ages from 3 days to 17 months were processed for histochemical analysis using Ulex europaeus and Grifforia simplifolica lectins as markers for pit and gland mucous cells, respectively. The dividing epithelial progenitors were identified by using immunohistochemical and electron microscopy techniques.


RESULTS
TFF1 loss was associated with amplification of both mucus-secreting pit and gland cells. Both lectins examined bound not only to mature mucous cells, but also to most of epithelial progenitors which gradually amplified with age and frequently were seen in mitosis. Analysis of 12- to 17-month-old TFF1-deficient stomachs revealed occasional groups of poorly differentiated mucosal cells with features similar to those of epithelial progenitors (or stem cells), in the basal portion of the antral mucosa. These cells eventually invaded the muscularis mucosa while maintaining some capacity to differentiate.


CONCLUSIONS
This study shows that the progenitors of pit and gland mucous cells contribute to gastric carcinogenesis in the pyloric antrum of TFF1 knockout mice, strongly supporting the concept of stem cell origin of cancer.
Karam
S M
SM
Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, andInstitute of Genetics and Molecular and Cellular Biology, Department of Cancer Biology, University of Louis Pasteur, Illkirch cedex, France.
Tomasetto
C
C
Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, andInstitute of Genetics and Molecular and Cellular Biology, Department of Cancer Biology, University of Louis Pasteur, Illkirch cedex, France.
Rio
M-C
MC
Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, andInstitute of Genetics and Molecular and Cellular Biology, Department of Cancer Biology, University of Louis Pasteur, Illkirch cedex, France.
D000375:Aging / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology* / Q000648:ultrastructure; D005753:Gastric Mucosa / Q000473:pathology / Q000648:ultrastructure; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000172:deficiency* / Q000378:metabolism; D011706:Pyloric Antrum / Q000473:pathology / Q000648:ultrastructure; D011708:Pylorus / Q000473:pathology / Q000648:ultrastructure; D013234:Stem Cells / Q000473:pathology* / Q000648:ultrastructure; D013274:Stomach Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D000071163:Trefoil Factor-1
D037102:Lectins; D010455:Peptides; C472724:Tff1 protein, mouse; D000071163:Trefoil Factor-1