Macrophage inflammatory protein-3alpha (mip-3alpha) promotes pancreatic cancer cell invasion by upregulation of matrix metalloproteinase-9 (MMP-9) production

Abstract

Introduction: MIP-3α has been shown to promote tumor cell migration by upregulation of MMPs. We hypothesize that MIP-3α, by binding to the transmembrane receptor CCR6, promotes pancreatic cancer invasion through the upregulation of MMP-9, a type IV collagenase that plays a crucial role in tumor progression. Methods: RT-PCR for MIP-3α was performed on PANC-1, human pancreatic adenocarcinoma cells. The effect of MIP-3α on MMP-9 production by PANC-1 cells was evaluated by Western analysis. Tumor cell invasion was evaluated using a modified Boyden chamber invasion assay. Results: RT-PCR confirmed the presence of MIP-3α in PANC-1 cells. MIP-3α stimulated the production of both latent and active forms of MMP-9 as demonstrated by Western analysis (see Figure). MIP-3α promoted a dose-dependent increase in pancreatic cancer cell invasion (see Table). TABLE—ABSTRACT 36Summation of Invasive Cells in Five[MIP-3α] ng/ml01050100Invasive cells9.0 ± 6.113.0 ± 2.616.7 ± 4.523.3 ± 5.0∗ Anti-CCR6 Ab and anti-MMP-9 Ab inhibited MIP-3α stimulated PANC-1 invasion of collagen to 37% and 35% of control, respectively (p < 0.05). Conclusion: MIP-3α, through its CCR6 receptor, causes a dose-dependent increase in tumor cell invasion by the upregulation of MMP-9. Molecular based therapy aimed at the inhibition of MIP-3α through the CCR6 receptor may serve as a future target to prevent tumor cell invasion in pancreatic adenocarcinoma.