PURPOSE: Macrophage inflammatory protein-3α (Mip-3α) is part of a family of chemotactic cytokines involved in recruiting inflammatory cells throughout the body. CCR6 is a G-protein-linked, seven-transmembrane receptor that is highly specific for Mip-3α. The role of Mip-3α has been well defined in several inflammatory conditions, but its role has not been well defined in neoplastic processes. Mip-3α has been shown to promote pancreatic cancer cell migration, but no studies have demonstrated the effect of Mip-3α on pancreatic cancer cell invasion. We hypothesize that Mip-3α and its CCR6 receptor promote pancreatic cancer cell invasion. MATERIALS AND METHODS: Immunohistochemical staining was performed for Mip-3α and CCR6 in pancreatic cancer tissue and the human pancreatic cancer cell line PANC-1. RNA was isolated from PANC-1 cancer cells, and the presence of Mip-3α messenger RNA in PANC-1 cancer cells was determined by reverse transcriptase polymerase chain reaction. PANC-1 cancer cell invasion of type IV collagen was evaluated in the presence of Mip-3α and anti-CCR6 antibody with the use of a modified Boyden chamber invasion assay. RESULTS: Co-localization of Mip-3α and its CCR6 receptor in pancreatic cancer was confirmed using immunohistochemical staining for Mip-3α and its CCR6 receptor and reverse transcriptase polymerase chain reaction for Mip-3α. Immunohistochemical staining of pancreatic cancer tissue and the PANC-1 cancer cell line showed positive staining for Mip-3α and its CCR6 receptor within the cancer cells. Staining was also positive for Mip-3α within stromal cells adjacent to the cancer cells in pancreatic cancer tissue. Reverse transcriptase polymerase chain reaction demonstrated the presence of Mip-3α messenger RNA within PANC-1 cancer cells. Invasion studies showed that increasing concentrations of Mip-3α promoted a dose-dependent increase in pancreatic cancer cell invasion of type IV collagen. The addition of 100 ng/mL of Mip-3α promoted a threefold increase in pancreatic cancer cell invasion over that of the control group. Anti-CCR6 antibody inhibited Mip-3α-stimulated PANC-1 cancer cell invasion of type IV collagen by 63%. DISCUSSION: Co-localization of Mip-3α and its CCR6 receptor promotes pancreatic cancer cell invasion of type IV collagen. This finding continues to highlight the importance that inflammation plays in the progression of pancreatic cancer. As the relationship between the inflammatory and neoplastic processes involved with pancreatic cancer becomes better defined, therapies targeting the inflammatory process may help prevent pancreatic cancer invasion and metastasis.
- Cancer invasion
- Macrophage inflammatory protein-3α
- Pancreatic cancer
ASJC Scopus subject areas
- Cancer Research