Background: Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, intravasation, and suppression of antitumor immune responses.
Materials and methods: Ten transgenic nude mice, ubiquitously expressing green fluorescent protein (GFP), were injected subcutaneously with the human pancreatic cancer cell line, BXPC3, stably expressing red fluorescent protein (RFP). GFP-expressing macrophages from the GFP mice with the subcutaneous BxPC3-RFP tumor were harvested and defined as "tumor-educated macrophages". Macrophages were also harvested from transgenic GFP mice (n=10) without tumors and identified as "naïve macrophages." The tumor-educated and naïve macrophages were then implanted into BxPC-3-RFP tumor-bearing non-transgenic nude mice and compared for their ability to enhance tumor progression.
Results: In the control group, without macrophage injection, the average primary tumor weighed 668 mg and only three mice (30%) developed peritoneal metastases, which averaged 72 mg. The naïve-macrophage group had an average tumor weight of 823 mg (p=0.51) and 50% developed peritoneal metastases, whose weight averaged 975 mg (p=0.029). The group treated with tumor-educated macrophages had an average primary tumor weight of 2095 mg (p=0.001) and 75% of mice developed peritoneal metastases, whose weight averaged 2135 mg (p=0.008).
Conclusion: These results suggest that macrophages influence tumors, and tumors influence macrophages, and tumor-educated promote tumor progression. Tumor-educated macrophages may be a target for therapy of metastatic cancer.