Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.
Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.
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人肿瘤细胞系中内皮糖蛋白 (CD105) 的差异表达和细胞质/膜分布：对细胞增殖调节的影响。
DOI：
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发表时间：
2005
影响因子：
5.2
通讯作者：
Giovanni A. Rossi
中科院分区：
文献类型：
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作者：
L. Postiglione;G. Domenico;M. Caraglia;M. Marra;G. Giuberti;L. D. Vecchio;S. Montagnani;M. Macrí;Eugenia Maria Bruno;A. Abbruzzese;Giovanni A. Rossi
内皮糖蛋白（CD 105，TGF-β受体复合物的辅助成分）的表达和分布在不同的人肿瘤细胞和其在细胞增殖中的作用进行了评价。我们检测了：1）16个人癌细胞系，2）8个人肉瘤细胞系，3）5个其他肿瘤细胞系。使用HECV（内皮细胞）作为内皮糖蛋白表达的阳性对照。正常人真皮成纤维细胞（NHDF）和293细胞（上皮肾细胞）分别用作结缔组织和上皮组织的正常对照。结果表明，CD 105在大多数人癌细胞中低表达（10/16），而在大多数人肉瘤细胞中高表达（7/8），并且在各种肿瘤细胞系中表达不同。这些数据反映了肿瘤细胞系的正常对应物，即NHDF和293细胞的内皮糖蛋白表达。然而，肉瘤细胞系中的CD 105水平，即使始终低于NHDF，也显著高于癌细胞中观察到的水平。有趣的是，CD 105在MDA-MB-453（乳腺癌）、NPA（甲状腺乳头状癌）、科洛-853（黑色素瘤）和SaOS-2（骨肉瘤）的细胞质中呈现强表达，但在它们的细胞膜上弱表达。这种差异表达在细胞质和膜上的一些肿瘤细胞，表明一个复杂的机制，这种蛋白质的易位。在软琼脂中的克隆生长的一些细胞系，其特征在于高CD 105表达的分析，显示了增加的集落形成潜力，拮抗了添加抗CD 105阻断mAb。结果表明内皮糖蛋白在人癌和肉瘤细胞中差异表达，并且其过表达调节人实体瘤细胞的增殖速率。此外，这些数据表明，CD 105参与调节人类实体恶性肿瘤中的TGF-β效应，因此它可能在肿瘤诊断和治疗中发挥重要作用。
Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.