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Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Polyamine metabolism and tumorigenesis in the Apc(Min/+) mouse
F G Berger1, D L Kramer, C W Porter
1Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA. berger@sc.edu
Abstract:
While polyamine homoeostasis is clearly important in maintenance of normal cell function, the roles of these cations, as well as the enzymes that regulate their metabolism, in the neoplastic process are not clear. In particular, the polyamine catabolic enzyme SSAT (spermidine/spermine N(1)-acetyltransferase) seems to have different roles in tumorigenesis, depending upon the particular system being analysed. In attempts to clarify the function of SSAT in tumour development, we have utilized the Apc(Min/+) mouse, which carries a mutant allele of the Apc (adenomatous polyposis coli) gene, rendering it susceptible to the formation of multiple adenomas in the small intestine and colon. Using genetically engineered animals (i.e. transgenic and knockout mice), we have shown that SSAT acts as a tumour promoter in the Apc(Min/+) model. Modulation of tumorigenesis is not associated with changes in tissue levels of either spermidine or spermine. These findings, along with those made in other animal models of cancer, have prompted us to propose that metabolic flux through the polyamine biosynthetic and catabolic pathways, and the consequent changes in levels of various metabolites within the cell (i.e. the metabolome), is critical to tumour development. The metabolic flux model represents a novel way of thinking about the role of polyamines in cell physiology and the neoplastic process.
Insights
The enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) promotes tumor development in a mouse model. Metabolic flux, not just polyamine levels, is critical for cancer progression.
Area of Science:
- Biochemistry
- Oncology
- Genetics
Background:
- Polyamines are essential for normal cell function, but their role in cancer is unclear.
- The polyamine catabolic enzyme SSAT (spermidine/spermine N(1)-acetyltransferase) has varied roles in tumorigenesis.
- The Apc(Min/+) mouse model develops intestinal and colon adenomas, making it suitable for studying tumor development.
Purpose of the Study:
- To clarify the function of SSAT in tumor development using the Apc(Min/+) mouse model.
- To investigate the relationship between SSAT activity, polyamine levels, and tumorigenesis.
- To propose a novel model for understanding polyamine metabolism in cancer.
Main Methods:
- Utilized genetically engineered Apc(Min/+) mice (transgenic and knockout) to study SSAT function.
- Analyzed the impact of SSAT modulation on tumor formation in the Apc(Min/+) model.
- Measured tissue levels of spermidine and spermine to assess polyamine homeostasis.
Main Results:
- SSAT acts as a tumor promoter in the Apc(Min/+) mouse model.
- Tumorigenesis modulation by SSAT was not linked to changes in spermidine or spermine levels.
- Findings suggest metabolic flux, rather than absolute polyamine concentrations, influences tumor development.
Conclusions:
- SSAT plays a significant role in promoting tumor development.
- Metabolic flux through polyamine pathways is critical for neoplastic processes.
- The metabolic flux model offers a new perspective on polyamine roles in cancer.
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