Detection and localization of MIP-3α/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer

Jörg Kleeff, Toshiyuki Kusama, Devora L. Rossi, Toshiyuki Ishiwata, Haruhisa Maruyama, Helmut Friess, Markus W. Büchler, Albert Zlotnik, Murray Korc

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129 Scopus citations


Macrophage Proinflammatory Human Chemokine-3α (Mip-3α/LARC/Exodus) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip- 3α signals through a recently identified G-protein linked 7-transmembrane receptor, CCR6. In this study, we have characterized the expression of Hip- 3α and CCR6 in 12 normal and 16 cancerous human pancreatic tissues and in 4 cultured pancreatic cancer cell lines, and assessed the effects of Mip-3α on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3α in comparison with normal pancreatic samples. By in situ hybridization Mip-3α and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3α was abundant in the macrophages infiltrating the tumor mass. Mip-3α and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell lines. Mip-3α stimulated the growth of one cell line, enhanced the migration of another cell line, and was without effect in the other 2 cell lines. Together, our findings suggest that Mip- 3α has the potential to act via autocrine and paracrine mechanisms to contribute to' the pathobiology of human pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)650-657
Number of pages8
JournalInternational Journal of Cancer
Issue number4
StatePublished - Jan 1 1999


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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