Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer.
Macrophage Proinflammatory Human Chemokine-3alpha (Mip-3alpha/LARC/Exodus) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip-3alpha signals through a recently identified G-protein linked 7-transmembrane receptor, CCR6. In this study, we have characterized the expression of Mip-3alpha 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-3alpha on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3alpha in comparison with normal pancreatic samples. By in situ hybridization Mip-3alpha and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3alpha was abundant in the macrophages infiltrating the tumor mass. Mip-3alpha and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell lines. Mip-3alpha 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-3alpha has the potential to act via autocrine and paracrine mechanisms to contribute to the pathobiology of human pancreatic cancer.
Kleeff
J
J
Department of Medicine, University of California, Irvine 92697, USA.
Kusama
T
T
Rossi
D L
DL
Ishiwata
T
T
Maruyama
H
H
Friess
H
H
Büchler
M W
MW
Zlotnik
A
A
Korc
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010179:Pancreas / Q000737:chemistry / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins