The expression of HMGB1 protein and its receptor RAGE in human malignant tumors
The expression of HMGB1 protein and its receptor RAGE in human malignant tumors
复制标题
DOI：
10.1007/s11010-009-0305-0
复制
发表时间：
2010-04-01
影响因子：
4.3
通讯作者：
Pasheva, Evdokia
中科院分区：
文献类型：
--
作者：
Kostova, Nora;Zlateva, Stanislava;Pasheva, Evdokia
高迁移率族蛋白1(High Mobility Group Box 1，HMGB1)是一种核内非组蛋白蛋白，可在细胞外介质中对多种刺激做出反应，参与肿瘤的发生。HMGB1在多种肿瘤类型中都有高水平的报道，但很少有数据将HMGB1与组织学分级或特定的细胞类型和细胞定位联系起来。我们研究了HMGB1蛋白在不同分化程度的人恶性肿瘤和肿瘤转移中的表达。在所有肿瘤组织中，蛋白质水平都升高。在中分化癌中，该蛋白定位于核周，而在低分化癌中，该蛋白有非特异性核定位的趋势。HMGB1蛋白及其受体RAGE被认为是一对配体-受体对，在调节肿瘤细胞的侵袭性方面发挥着重要作用。并不是所有被测试的肿瘤标本都产生RAGE。我们发现在肝细胞癌、结直肠癌和乳腺筛状癌中高水平表达，但在恶性睾丸标本中不表达。可能，RAGE的合成与不同的肿瘤类型有关。在转移细胞中，RAGE表现出较高的表达水平，失去了原发肿瘤特有的颗粒状胞浆模式。
High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein discovered to be released in the extracellular medium as a response to various stimuli and implicated in cancerogenesis. High HMGB1 levels are reported in a variety of tumor types, but there are few data relating HMGB1 to the histological grade or to a particular cell type and cellular localization. We studied the expression of HMGB1 protein in malignant human tumors of different differentiation level and in tumor metastasis. In all tumor tissues, the protein level is elevated. In moderately differentiated carcinomas, the localization of the protein is perinuclear, while in the low differentiated; there is a tendency for non-specific nuclear localization. HMGB1 protein and its receptor RAGE are identified as a ligand-receptor pair that plays an important role in regulating the invasiveness of tumor cells. RAGE is not produced in all of the tested tumor specimens. We found high level of expression in hepatocellular, colorectal, and breast cribriform carcinomas, but not in malignant testicular specimens. Probably, the RAGE synthesis is related to distinctive tumor types. In metastatic cells, RAGE exhibits higher level of expression losing its specific granular cytosolic pattern characteristic for the primary tumors.