Macrophage inflammatory protein-3α promotes pancreatic cancer cell invasion

Amy S. Campbell, Daniel Albo, Troy F. Kimsey, Stephanie L. White, Thomas N. Wang

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Human CC chemokine Macrophage Inflammatory Protein-3α (MIP-3α) directs inflammatory cell migration through its binding to the transmembrane receptor CCR6. MIP-3α has recently been shown to promote tumor cell migration in pancreatic adenocarcinoma by up-regulation of matrix metalloproteinases (MMPs). We hypothesized that MIP-3α promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase. Immunohistochemistry and RT-PCR confirmed the presence of MIP-3α in PANC-1 cells, a human pancreatic adenocarcinoma cell line. MIP-3α 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-3α promoted a dose-dependent increase in pancreatic cancer cell invasion (P < 0.05) at 100 ng/ml. The activity at the putative MIP-3α receptor, CCR6, was demonstrated by receptor blockade. Anti-CCR6 antibody and anti-MMP-9 antibody inhibited MIP-3α-stimulated PANC-1 cell invasion of collagen to 37% and 35% of control, respectively (P < 0.05). MIP-3α, through its CCR6 receptor, promotes tumor cell invasion by the up-regulation of MMP-9. Molecular based therapy aimed at the inhibition of MIP-3α activity through the CCR6 receptor may serve as a future target to prevent tumor cell invasion in pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)96-101
Number of pages6
JournalJournal of Surgical Research
Volume123
Issue number1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Macrophage Inflammatory Proteins
Pancreatic Neoplasms
CCR6 Receptors
Matrix Metalloproteinase 9
Adenocarcinoma
Up-Regulation
Cell Movement
Neoplasms
CC Chemokines
Collagenases
Matrix Metalloproteinases
Anti-Idiotypic Antibodies
Collagen
Immunohistochemistry

Keywords

  • CCR6
  • macrophage inflammatory protein-3α
  • matrix metalloproteinase
  • pancreatic adenocarcinoma

ASJC Scopus subject areas

  • Surgery

Cite this

Macrophage inflammatory protein-3α promotes pancreatic cancer cell invasion. / Campbell, Amy S.; Albo, Daniel; Kimsey, Troy F.; White, Stephanie L.; Wang, Thomas N.

In: Journal of Surgical Research, Vol. 123, No. 1, 01.01.2005, p. 96-101.

Research output: Contribution to journalArticle

Campbell, Amy S. ; Albo, Daniel ; Kimsey, Troy F. ; White, Stephanie L. ; Wang, Thomas N. / Macrophage inflammatory protein-3α promotes pancreatic cancer cell invasion. In: Journal of Surgical Research. 2005 ; Vol. 123, No. 1. pp. 96-101.
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