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

Macrophage Proinflammatory Human Chemokine-3 alpha (Mip-3 alpha/LARC/Exodus ) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip-3 alpha signals through a recently identified G-protein linked ir-transmembr ane receptor, CCR6. In this study, we have characterized the expression of Mip-3 alpha and CCR6 in 12 normal and 16 cancerous human pancreatic tissues and in 4 cultured pancreatic cancer cell lines, and assessed the effects o f Mip-3 alpha on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3 alpha in comparison with normal pancr eatic: samples. By in situ hybridization Mip-3 alpha and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3 alpha w as abundant in the macrophages infiltrating the tumor mass. Mip-3 alpha and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell li nes. Mip-3 alpha stimulated the growth of one cell line, enhanced the migra tion of another cell line, and was without effect: in the other 2 cell line s, Together, our findings suggest that Mip-3a: has the potential to act via autocrine and paracrine mechanisms to contribute to the pathobiology of hu man pancreatic cancer. (C) 1999 Wiley-Liss, Inc.