Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis
Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis
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DOI：
10.1023/a:1025821229013
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Mukai, K
中科院分区：
文献类型：
--
作者：
Iwaya, K;Ogawa, H;Mukai, K
β -连环蛋白参与细胞外基质的细胞运动，并在正常和肿瘤间充质细胞中表达。为了阐明β -catenin在细胞质和/或细胞核中的表达是否与骨肉瘤肺转移倾向相关，我们将具有高肺转移潜力的LM8小鼠骨肉瘤细胞系与原始Dunn细胞在β -catenin表达水平方面进行了比较。两种骨肉瘤细胞系都失去了β -连环蛋白的膜定位。通过直接序列分析，β -连环蛋白基因3外显子未发生突变。大量LM8细胞显示弥漫的细胞质和/或核染色β -catenin (30.8 / HPF)，而较少数量的Dunn细胞表达β -catenin （7.7 / HPF）。β -连环蛋白染色阳性的细胞常见于浸润前和肺转移灶内静脉内的肿瘤沉积。因此，通过免疫印迹分析判断，LM8细胞比Dunn细胞表达更多的β -连环蛋白。在5例切除的肺转移病例中，检测到β -catenin易位到骨肉瘤细胞的细胞质和/或细胞核，尽管7例未转移超过5年的原发性骨肉瘤细胞未显示β -catenin表达。这些数据表明，β -连环蛋白的细胞质和/或细胞核染色是骨肉瘤肺转移潜力的生物学标志物。
Beta-catenin is involved in cell motility in the extracellular matrix, and is expressed in normal and neoplastic mesenchymal cells. In order to clarify whether beta-catenin expression in the cytoplasm and/or nucleus is associated with a propensity for pulmonary metastasis in osteosarcoma, the LM8 murine osteosarcoma cell line with a high metastatic potential to the lung was compared with original Dunn cells in terms of the beta-catenin expression level. Both osteosarcoma cell lines lost membrane localization of beta-catenin. However, beta-catenin gene had no mutation in exon 3 by direct sequence analysis. A large number of LM8 cells showed diffuse cytoplasmic and/or nuclear staining of beta-catenin (30.8 per high power field (HPF)), while a much smaller number of Dunn cells showed expression of beta-catenin (7.7 per HPF). Cells with positive staining of beta-catenin were frequently seen at the invasive front and in intravenous tumor deposits within the metastatic lesions to the lung. Thus, LM8 cells express a larger amount of the beta-catenin protein than Dunn cells, as judged by immunoblot analysis. In five resected cases of pulmonary metastasis, translocation of beta-catenin to the cytoplasm and/or nucleus of osteosarcoma cells was detected, although seven primary osteosarcomas cells that did not metastasize for more than five years did not show beta-catenin expression. These data indicate that the cytoplasmic and/or nuclear staining of beta-catenin is a biological marker of metastatic potential of osteosarcoma to the lung.