Human osteosarcoma expresses specific ephrin profiles - Implications for tumorigenicity and prognosis

Human osteosarcoma expresses specific ephrin profiles - Implications for tumorigenicity and prognosis
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DOI:
10.1002/cncr.10749
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发表时间:
2002-08-15
期刊:
影响因子:
6.2
通讯作者:
Clayer, M
Clayer, M
中科院分区:
医学1区
文献类型:
--
作者:
Varelias, A;Koblar, SA;Clayer, M

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背景骨肉瘤恶性的分子机制尚不清楚。据报道,在乳腺癌和黑色素瘤患者中,Eph受体蛋白酪氨酸激酶及其配体ephrin与致瘤性增加相关。Eph/ephrins在人骨肉瘤中的表达和作用尚不明确。应用逆转录聚合酶链反应(RT-PCR)技术检测了9例人骨肉瘤组织和5株人骨肉瘤细胞系中ephrin-A1、ephrin-A3、ephrin-A4、ephrin-A5、ephrin-B1、ephrin-B2和ephrin-B3 mRNA的表达。免疫组化法检测人骨肉瘤组织中Ephrin-B1蛋白的表达。骨肉瘤标本与其ephrin表达谱之间存在临床病理相关性。正常骨标本、骨肉瘤组织标本和骨肉瘤细胞系表达不同的肝配蛋白-A1、肝配蛋白-A4和肝配蛋白-B2 mRNA谱。第二种mRNA谱包括肝配蛋白-A3、肝配蛋白-A5和肝配蛋白-B1,由肿瘤亚组表达。ephrin-B1的表达与临床预后不良相关。Ephrin-B1蛋白在骨肉瘤细胞和血管中均有表达。这项研究的结果表明,ephrin-B1表达的骨肉瘤可能是一个不良的预后标志物,通过增加致瘤性。(C)2002年美国癌症协会。
BACKGROUND. The molecular mechanisms underlying malignancy of osteosarcoma are unknown. It has been reported that eph receptor protein tyrosine kinases and their ligands, ephrins, are associated with increased tumorigenicity in patients with breast carcinoma and melanoma. The expression and role of eph/ephrins in human osteosarcoma has not yet been characterized.METHODS. Ephrin-A1, ephrin-A3, ephrin-A4, ephrin-A5, ephrin-B1, ephrin-B2, and ephrin-B3 mRNA expression was examined by reverse transcription polymerase chain reaction analysis in nine specimens of human osteosarcoma tissue and five human osteosarcoma cell lines. Ephrin-B1 protein expression was detected immunohistochemically in human osteosarcoma tissue. Clinicopathologic correlation was made between the osteosarcoma specimens and their ephrin expression profiles.RESULTS. Normal bone specimens, osteosarcoma tissue specimens, and osteosarcoma cell lines expressed a distinct mRNA profile of ephrin-A1, ephrin-A4, and ephrin-B2. A second mRNA profile that included ephrin-A3, ephrin-A5, and ephrin-B1 was expressed by a subset of tumors. The expression of ephrin-B1 was correlated with a poorer clinical prognosis. Ephrin-B1 protein was expressed by osteosarcoma cells and blood vessels.CONCLUSIONS. The results of this study suggest that ephrin-B1 expressed by osteosarcoma may be a poor prognostic marker through increased tumorigenicity. (C) 2002 A merican Cancer Society.