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Updated: Feb 8, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Identification of PGAM1 as a putative therapeutic target for pancreatic ductal adenocarcinoma metastasis using
Xinlu Liu1, Yejing Weng2, Peng Liu1
1First Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
Background:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal cancer characterized by an extremely low survival rate because of early metastasis. Identifying satisfactory therapeutic targets associated with metastasis is crucial to improve the treatment effect of PDAC.
Materials And Methods:
In this research, we used stable isotope labeling by amino acids in cell culture, 1-dodecyl-3-methylimidazolium chloride-assisted sample preparation method preparing protein sample and nano-reversed-phase liquid chromatography-mass spectrometry/mass spectrometry analysis to perform the comparative proteomics of two homologous hamster pancreatic cancer cell lines that are different in metastatic ability: PC-1.0 (highly metastatic) and PC-1 (weakly metastatic). Verifications are through immunohistochemistry on clinical human PDAC pathologic tissues as well as by Western blot of human pancreatic cancer cell lines. siRNA silencing methods were used to study the effect of molecules on invasion and metastasis of pancreatic cancer cell lines.
Results:
Bioinformatic analysis indicated that a total of 141 differentially expressed proteins (82 upregulated and 59 downregulated in PC-1.0 cells) were identified showing obviously differential expression (>1.5-fold change). These differentially expressed proteins were involved in a number of different biologic functions, metabolic pathways, and pathophysiologic processes. Phosphoglycerate mutase 1 (PGAM1) and HSPE1 are the top two upregulated proteins, and PDIA3 and CALR are the top two downregulated proteins in PC-1.0 cells compared to PC-1 cells. PGAM1 and HSPE1 showed higher expressions in PDAC tissue with clinical metastasis and highly metastatic pancreatic cancer cell lines PC-1.0 and Aspc-1. PDIA3 and CALR showed higher expressions in weakly metastatic pancreatic cancer cell lines PC-1 and Capan-2. The Western blot results were consistent with the MS quantification data. Silencing PGAM1 was found to decrease the migration and invasion of pancreatic cancer cell lines with statistical significance, especially in highly metastatic PC-1.0 and Aspc-1 cell lines.
Conclusion:
These data indicated that PGAM1 may be a potential therapeutic target for PDAC metastasis.
Insights
Pancreatic cancer metastasis is driven by proteins like PGAM1. Targeting PGAM1 could be a new therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC) treatment.
Area of Science:
- Proteomics
- Cancer Biology
- Metastasis Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with poor survival rates due to early metastasis.
- Effective therapeutic targets for PDAC metastasis are urgently needed to improve patient outcomes.
Purpose of the Study:
- To identify differentially expressed proteins associated with pancreatic cancer metastasis using comparative proteomics.
- To investigate the role of specific proteins in the invasion and metastasis of pancreatic cancer cells.
Main Methods:
- Comparative proteomic analysis of highly metastatic (PC-1.0) and weakly metastatic (PC-1) hamster pancreatic cancer cell lines using mass spectrometry.
- Validation of protein expression in human PDAC tissues and cell lines via immunohistochemistry and Western blot.
- Functional investigation of protein roles in cell migration and invasion using siRNA silencing.
Main Results:
- 141 differentially expressed proteins were identified between metastatic and non-metastatic cell lines.
- Phosphoglycerate mutase 1 (PGAM1) was significantly upregulated in highly metastatic cells and PDAC tissues.
- Silencing PGAM1 reduced the migration and invasion capabilities of pancreatic cancer cell lines.
Conclusions:
- PGAM1 is identified as a potential therapeutic target for inhibiting PDAC metastasis.
- These findings offer a basis for developing novel anti-metastatic therapies for pancreatic cancer.
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