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Updated: Feb 25, 2026
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice
Perparim Limani1, Michael Linecker, Marcel A Schneider
1*Department of Surgery and Transplantation, Swiss Hepato-pancreato-biliary (HPB) and Transplantation Laboratory, University Hospital Zurich, Zurich, Switzerland †Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA ‡Institute of Supramolecular Science and Engineering, University of Strasbourg, Strasbourg, France.
Objective:
To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer.
Background:
Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown.
Methods:
ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements.
Results:
ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d).
Conclusions:
Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.
Insights
Myo-Inositoltrispyrophosphate (ITPP) reduces colon cancer metastasis and improves survival in mice. Combining ITPP with chemotherapy further enhances these anti-cancer effects, suggesting potential for clinical trials.
Area of Science:
- Oncology
- Cancer Metastasis Research
- Hypoxia and Cancer
Background:
- Colorectal cancer is a leading cause of cancer death, with distant metastases occurring in 50% of patients.
- Tumor hypoxia is a critical factor in the development of metastases.
- Myo-Inositoltrispyrophosphate (ITPP) is a novel antihypoxic agent showing promise in experimental cancer models.
Purpose of the Study:
- To investigate the efficacy of ITPP in preventing distant metastases in a primary colon cancer model.
- To evaluate the combined effects of ITPP and FOLFOX chemotherapy on tumor progression and survival.
Main Methods:
- A mouse model of syngeneic colorectal cancer was established using green fluorescent protein-labeled cells.
- Tumor growth and metastasis were monitored using MRI and fluorescence detection of circulating tumor cells.
- Serum markers of tumor spread and animal survival were assessed.
Main Results:
- ITPP significantly reduced metastasis and indicators of tumor aggressiveness.
- A decrease in circulating tumor cells and malignant serum markers (osteopontin, Cxcl12) was observed.
- ITPP treatment led to a significant survival benefit, which was maximized when combined with FOLFOX chemotherapy.
Conclusions:
- Restoring oxygen levels with ITPP inhibits colon cancer spread and improves survival.
- The combination of ITPP and chemotherapy offers enhanced therapeutic benefits.
- These findings support the initiation of clinical trials for ITPP in colorectal cancer patients.
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