Begley Lesa A, Kasina Sathish, Mehra Rohit, Adsule Shreelekha, Admon Andrew J, Lonigro Robert J, Chinnaiyan Arul M, Macoska Jill A
Department of Urology, University of Michigan, Ann Arbor, MI 48109-0944, USA.
Neoplasia. 2008 Mar;10(3):244-54. doi: 10.1593/neo.07976.
CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate.
CXCL5是一种促血管生成的CXC型趋化因子,它是一种炎症介质,也是粒细胞免疫细胞的强效趋化剂。与许多其他趋化因子不同,CXCL5由免疫细胞(中性粒细胞、单核细胞和巨噬细胞)和非免疫细胞(上皮细胞、内皮细胞和成纤维细胞)分泌。本研究旨在确定在正常和恶性人前列腺组织中,这些细胞类型中的哪些表达CXCL5,表达水平是否与恶性程度相关,以及CXCL5是否刺激与良性或恶性前列腺上皮表型一致的生物学效应。这些研究结果表明,CXCL5蛋白表达水平与前列腺肿瘤进展一致,与炎症浸润高度相关,并且在良性和恶性前列腺腺管腔中经常检测到。外源性给予CXCL5可刺激未转化和转化的前列腺上皮细胞的细胞增殖和基因转录,并诱导高侵袭性前列腺癌细胞在体外穿过合成基底膜。这些发现表明,炎症介质CXCL5可能在前列腺良性和恶性增殖性疾病的病因学中发挥多种作用。