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Updated: Jul 7, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Hematopoietic prostaglandin D synthase suppresses intestinal adenomas in ApcMin/+ mice
Jae Man Park1, Yoshihide Kanaoka, Naomi Eguchi
1Division of Medical Genetics, Department of Pediatrics and Department of Pathology, Los Angeles Biomedical Research Institute, Harbor-University of California-Los Angeles Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA.
Abstract:
Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE(2) promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD(2) may suppress tumors, but a role for biosynthetic enzymes for PGD(2) in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in Apc(Min/+) mice led to approximately 50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, Apc(Min/+) mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11beta-PGF(2alpha) and a lower excretion of a PGE(2) metabolite in transgenic mice, but differences (30-40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE(2) or inhibition of the nuclear factor-kappaB cascade by PGD(2) metabolites.
Insights
Hematopoietic prostaglandin D synthase (PGD2) inhibits intestinal tumor development. Disrupting its gene increased tumors by 50%, while its overexpression reduced them by 80% in mouse models.
Area of Science:
- Molecular Biology
- Cancer Research
- Immunology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin prevent colon cancer by inhibiting prostaglandin (PG) synthesis.
- Prostaglandin E2 (PGE2) is known to promote colon neoplasia.
- Previous research suggested prostaglandin D2 (PGD2) might suppress tumors, but its biosynthetic enzymes' role was unstudied.
Purpose of the Study:
- To investigate the role of hematopoietic PGD synthase in intestinal tumor development.
- To determine if PGD2 synthesis influences the number and size of intestinal adenomas.
Main Methods:
- Used Apc(Min/+) mouse models with gene knockout or transgenic expression of hematopoietic PGD synthase.
- Analyzed intestinal adenoma formation (number and size) in modified mice compared to controls.
- Utilized immunohistochemistry to detect enzyme localization in gut mucosa and measured urinary PG metabolite excretion.
Main Results:
- Mice lacking hematopoietic PGD synthase had approximately 50% more intestinal adenomas.
- Mice with transgenic human hematopoietic PGD synthase showed an 80% reduction in intestinal adenomas.
- Hematopoietic PGD synthase was primarily found in macrophages and monocytes within the gut mucosa.
Conclusions:
- Hematopoietic PGD synthase plays a significant inhibitory role in intestinal tumor development.
- Further research is needed to elucidate the precise mechanisms, potentially involving PGE2 pathway modulation or NF-kappaB inhibition.
