Related Experiment Video
Updated: Aug 20, 2026
Growing Desmoplastic Three-Dimensional Pancreatic Cancer Spheroids from Co-Culture
Published on: September 27, 2024
Macrophage inflammatory protein-3alpha promotes pancreatic cancer cell invasion
Amy S Campbell1, Daniel Albo, Troy F Kimsey
1Department of General Surgery, Section of Surgical Oncology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Background:
Human CC chemokine Macrophage Inflammatory Protein-3alpha (MIP-3alpha) directs inflammatory cell migration through its binding to the transmembrane receptor CCR6. MIP-3alpha has recently been shown to promote tumor cell migration in pancreatic adenocarcinoma by up-regulation of matrix metalloproteinases (MMPs). We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase.
Materials, Methods, And Results:
Immunohistochemistry and RT-PCR confirmed the presence of MIP-3alpha in PANC-1 cells, a human pancreatic adenocarcinoma cell line. MIP-3alpha stimulated the production of both latent and active forms of MMP-9 in PANC-1 by Western analysis. Tumor cell invasion was then evaluated using a modified Boyden chamber invasion assay. MIP-3alpha promoted a dose-dependent increase in pancreatic cancer cell invasion (P < 0.05) at 100 ng/ml. The activity at the putative MIP-3alpha receptor, CCR6, was demonstrated by receptor blockade. Anti-CCR6 antibody and anti-MMP-9 antibody inhibited MIP-3alpha-stimulated PANC-1 cell invasion of collagen to 37% and 35% of control, respectively (P < 0.05).
Conclusions:
MIP-3alpha, through its CCR6 receptor, promotes tumor cell invasion by the up-regulation of MMP-9. Molecular based therapy aimed at the inhibition of MIP-3alpha activity through the CCR6 receptor may serve as a future target to prevent tumor cell invasion in pancreatic adenocarcinoma.
Insights
Macrophage Inflammatory Protein-3alpha (MIP-3alpha) promotes pancreatic cancer invasion by increasing MMP-9 production via the CCR6 receptor. Inhibiting this pathway may prevent tumor spread.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Macrophage Inflammatory Protein-3alpha (MIP-3alpha) is a CC chemokine that regulates inflammatory cell migration via the CCR6 receptor.
- MIP-3alpha has been implicated in promoting pancreatic adenocarcinoma cell migration through matrix metalloproteinase (MMP) up-regulation.
Purpose of the Study:
- To investigate the role of MIP-3alpha in pancreatic cancer invasion.
- To determine if MIP-3alpha promotes invasion via up-regulation of MMP-9, a specific Type 4 collagenase.
Main Methods:
- Immunohistochemistry and RT-PCR were used to detect MIP-3alpha in PANC-1 cells.
- Western analysis assessed MMP-9 production stimulated by MIP-3alpha.
- A modified Boyden chamber assay evaluated tumor cell invasion.
- Receptor blockade with anti-CCR6 and anti-MMP-9 antibodies was employed.
Main Results:
- MIP-3alpha was confirmed in PANC-1 cells and stimulated both latent and active MMP-9 production.
- MIP-3alpha significantly increased pancreatic cancer cell invasion in a dose-dependent manner.
- Blocking CCR6 or MMP-9 activity substantially inhibited MIP-3alpha-induced invasion.
Conclusions:
- MIP-3alpha, acting through the CCR6 receptor, enhances pancreatic tumor cell invasion by up-regulating MMP-9.
- Targeting the MIP-3alpha/CCR6 pathway offers a potential therapeutic strategy to inhibit pancreatic cancer invasion.
Related Concept Videos
01:35Cancer Cell Migration through Invadopodia
01:21Acute Pancreatitis II: Pathophysiology