Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate
Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate
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DOI：
10.1002/path.1476
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发表时间：
2004-01-01
影响因子：
7.3
通讯作者：
De Miguel, MP
中科院分区：
文献类型：
--
作者：
Royuela, M;Ricote, M;De Miguel, MP
白细胞介素-6（IL-6）及其受体与前列腺癌进展有关。由于IL-6家族的其他成员，如白血病抑制因子（LIF）和抑瘤素M（OSM）共享gp 130，其受体的信号转导亚基，不考虑这些细胞因子及其特异性受体亚基的表达的数据的解释可能是误导。研究了IL-6家族及其受体亚单位在正常前列腺、良性前列腺增生（BPH）和前列腺癌（PC）中的免疫组化模式。在正常前列腺中，gp 130和OSMR α仅在间质中检测到，LIFR β非常罕见。虽然IL-6几乎不免疫定位于上皮的基底细胞，但在基质中检测到OSM，并且在上皮和基质中均检测到LIF。这表明正常前列腺基质中的细胞因子家族具有自分泌作用。在BPH中，gp 130和OSMR α在上皮和间质中均被检测到，而LIFR β仅定位于上皮。IL-6优先定位于上皮，OSM定位于基质，LIF定位于两个隔室。因此，除了在间质中的自分泌作用外，IL-6和OSM可能在BPH中从间质到上皮中发挥旁分泌作用。在PC中，gp 130和OSMR α均在上皮和间质中检测到，随着Gleason分级的升高而增加，而LIFR β仅定位于低Gleason分级癌的上皮。IL-6、LIF和OSM定位于所有细胞类型，免疫染色随Gleason分级而增加。这些数据表明，这些细胞因子在PC的上皮细胞中的自分泌作用。LIFR β仅在低Gleason级别癌症中表达的独特模式使LIFR β成为恶性肿瘤诊断的候选者。OSM主要在高Gleason分级癌中的作用使OSM成为前列腺癌治疗的假定靶点。版权所有（C）2003约翰威利父子有限公司。
Interleukin-6 (IL-6) and its receptor have been implicated in prostate cancer progression. Because other members of the IL-6 family such as leukaemia inhibitory factor (LIF) and oncostatin M (OSM) share gp130, the signal transduction subunit of their receptors, interpretation of the data without considering the expression of these cytokines and their specific receptor subunits could be misleading. The immunohistochemical pattern of the IL-6 family and their receptor subunits in normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PC) was investigated. In normal prostates, gp130 and OSMRalpha were detected exclusively in the stroma and LIFRbeta was very scarce. While IL-6 was scarcely immunolocalized to the basal cells of the epithelium, OSM was detected in the stroma and LIF in both the epithelium and the stroma. This suggests an autocrine role for this family of cytokines in the stroma of normal prostates. In BPH, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, whereas LIFRbeta was localized only to the epithelium. IL-6 localized preferentially to the epithelium, OSM to the stroma, and LIF to both compartments. Therefore, in addition to the autocrine role in the stroma, IL-6 and OSM may play a paracrine role from the stroma to the epithelium in BPH. In PC, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, increasing with rising Gleason grade, whereas LIFRbeta was localized exclusively to the epithelium of low Gleason grade carcinomas. IL-6, LIF, and OSM localized in all cell types, with immunostaining increasing with Gleason grade. These data suggest an autocrine role for these cytokines in the epithelial cells of PC. The distinct pattern of expression of LIFRbeta exclusively in low Gleason grade carcinomas makes LIFRbeta a candidate for malignancy diagnosis. The role of OSM mainly in high Gleason grade carcinomas makes OSM a putative target for prostate cancer therapy. Copyright (C) 2003 John Wiley Sons, Ltd.