Kleeff J, Kusama T, Rossi D L, Ishiwata T, Maruyama H, Friess H, Büchler M W, Zlotnik A, Korc M
Department of Medicine, University of California, Irvine 92697, USA.
Int J Cancer. 1999 May 17;81(4):650-7. doi: 10.1002/(sici)1097-0215(19990517)81:4<650::aid-ijc23>3.0.co;2-#.
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.
巨噬细胞炎性人类趋化因子-3α（Mip-3α/LARC/Exodus）属于一大类趋化细胞因子家族，它们参与引导炎性细胞迁移并调节血管生成。Mip-3α通过最近鉴定出的G蛋白偶联7跨膜受体CCR6发出信号。在本研究中，我们已对12例正常人类胰腺组织、16例癌性人类胰腺组织以及4种培养的胰腺癌细胞系中Mip-3α和CCR6的表达进行了特征描述，并评估了Mip-3α对这些细胞系生长和侵袭的影响。与正常胰腺样本相比，胰腺癌组织中Mip-3α明显过表达。通过原位杂交发现，肿瘤内的癌细胞中存在Mip-3α和CCR6 mRNA部分。此外，浸润肿瘤块的巨噬细胞中Mip-3α含量丰富。在所有4种测试的胰腺癌细胞系中均表达Mip-3α及其受体CCR6。Mip-3α刺激了一种细胞系的生长，增强了另一种细胞系的迁移能力，而对另外2种细胞系没有影响。总之，我们的研究结果表明，Mip-3α有可能通过自分泌和旁分泌机制对人类胰腺癌的病理生物学产生影响。
