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Macrophages on the Peritoneum are involved in Gastric Cancer Peritoneal Metastasis
Hongjiang Song1, Tie Wang1, Lining Tian2
1Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
Abstract:
Tumor-associated macrophages (TAM) have been shown to support tumor growth and progression by various mechanisms. However, the roles of TAM in gastric cancer (GC) peritoneal metastasis remain elusive. To explore the roles of macrophages in the process of GC peritoneal metastasis, we performed the present study. Samples from the primary GC tumor beds, surgical margins, peritoneal metastatic lesions and surrounding tissue, and the Pouch of Douglas, were collected, fixed by formalin, and embedded with paraffin. Immunohistochemistry staining for macrophages markers was performed. The peritoneal lavage was obtained from a fraction of patients to analyze the ratios of epidermal growth factor (EGF)- and vascular endothelial growth factor (VEGF)-secreting macrophages in the peritoneal cavity. GC patients with peritoneal metastasis had increased levels of macrophages and alternatively activated macrophages in the peritoneum compared to those without dissemination. Patients bearing more macrophages in the peritoneum had a poorer prognosis. GC patients bearing peritoneal metastasis harbored an increased level of angiogenesis. Macrophages in the peritoneal cavity were a source of EGF and VEGF. Macrophages in the peritoneum of GC patients play a supportive role for peritoneal metastasis by producing EGF and VEGF. Macrophages in the peritoneum might be a therapeutic target in the future.
Insights
Tumor-associated macrophages (TAM) promote gastric cancer (GC) peritoneal metastasis by secreting EGF and VEGF. Targeting these macrophages in the peritoneum could be a future therapeutic strategy for GC patients.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Tumor-associated macrophages (TAM) influence tumor progression.
- The specific role of TAM in gastric cancer (GC) peritoneal metastasis is not well understood.
Purpose of the Study:
- To investigate the role of macrophages in GC peritoneal metastasis.
- To determine if peritoneal macrophages contribute to GC dissemination and angiogenesis.
Main Methods:
- Analysis of patient samples including primary tumors, peritoneal lesions, and surrounding tissues.
- Immunohistochemistry for macrophage markers.
- Peritoneal lavage analysis for EGF and VEGF-secreting macrophages.
Main Results:
- Increased macrophage levels, particularly alternatively activated macrophages, in the peritoneum of GC patients with metastasis.
- Higher peritoneal macrophage density correlated with poorer prognosis and increased angiogenesis.
- Peritoneal macrophages were identified as a source of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF).
Conclusions:
- Macrophages in the peritoneal cavity support GC peritoneal metastasis through EGF and VEGF production.
- Peritoneal macrophages represent a potential therapeutic target for managing GC peritoneal spread.
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