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Updated: Oct 18, 2025
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
Metabolomic Detection Between Pancreatic Cancer and Liver Metastasis Nude Mouse Models Constructed by Using the
Shuo Wang1, Jiang Chen1, Hongyu Li1
1General Hospital of Northern Theater Command of China Medical University, Shenyang, Liaoning Province, P.R. China.
Abstract:
Background: Pancreatic cancer (PC) has a poor prognosis and is prone to liver metastasis. The KAI1/CD82 gene inhibits PC metastasis. This study aimed to explore differential metabolites and enrich the pathways in serum samples between PC and liver metastasis nude mouse models stably expressing KAI1/CD82. Methods: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed for the first time. This cell line was used to construct 3 PC nude mouse models and 3 liver metastasis nude mouse models. The different metabolites and Kyoto encyclopedia of genes and genomes (KEGG) and human metabolome database (HMDB) enrichment pathways were analyzed using the serum samples of the 2 groups of nude mouse models on the basis of untargeted ultra-performance liquid chromatography-tandem mass spectrometry platform. Results: KAI1/CD82-PLV-EF1α-MCS-IRES-Puro vector and PANC1 cell line stably expressing KAI1/CD82 were constructed successfully, and all nude mouse models survived and developed cancers. Among the 1233 metabolites detected, 18 metabolites (9 upregulated and 9 downregulated) showed differences. In agreement with the literature data, the most significant differences between both groups were found in the levels of bile acids (taurocholic acid, chenodeoxycholic acid), glycine, prostaglandin E2, vitamin D, guanosine monophosphate, and inosine. Bile recreation, primary bile acid biosynthesis, and purine metabolism KEGG pathways and a series of HMDB pathways (P < .05) contained differential metabolites that may be associated with liver metastasis from PC. However, the importance of these metabolites on PC liver metastases remains to be elucidated. Conclusions: Our findings suggested that the metabolomic approach may be a useful method to detect potential biomarkers in PC.
Insights
This study identified distinct metabolic profiles in pancreatic cancer (PC) liver metastasis models. These findings suggest metabolomics can help detect potential PC biomarkers for liver metastasis.
Area of Science:
- Metabolomics
- Cancer Metastasis
- Molecular Biology
Background:
- Pancreatic cancer (PC) exhibits poor prognosis and a high propensity for liver metastasis.
- The KAI1/CD82 gene is known to inhibit PC metastasis.
- Understanding the metabolic changes associated with PC liver metastasis is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate differential metabolites and enriched pathways in serum samples from PC and liver metastasis nude mouse models.
- To analyze the role of KAI1/CD82 in modulating the metabolomic profile of PC liver metastasis.
- To identify potential serum biomarkers for PC liver metastasis.
Main Methods:
- Construction of stably KAI1/CD82-expressing PANC1 cell lines and subsequent nude mouse models for PC and liver metastasis.
- Untargeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis of serum samples.
- Bioinformatic analysis including KEGG and HMDB pathway enrichment to identify differential metabolites.
Main Results:
- Successful construction of KAI1/CD82-expressing cell lines and viable mouse models.
- Identification of 18 differentially abundant metabolites (9 upregulated, 9 downregulated) between PC and liver metastasis groups.
- Significant alterations observed in bile acids, glycine, prostaglandin E2, vitamin D, guanosine monophosphate, and inosine levels.
- Enrichment of pathways including bile recreation, primary bile acid biosynthesis, and purine metabolism associated with liver metastasis.
Conclusions:
- The metabolomic approach is a valuable tool for identifying potential biomarkers in pancreatic cancer.
- Specific metabolites and pathways identified may play a role in PC liver metastasis.
- Further research is needed to elucidate the precise role of these metabolites in PC liver metastasis progression.
