High expression of the Met receptor in prostate cancer metastasis to bone

High expression of the Met receptor in prostate cancer metastasis to bone
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DOI:
10.1016/s0090-4295(02)01954-4
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发表时间:
2002-12-01
期刊:
影响因子:
2.1
通讯作者:
Woude, GFV
Woude, GFV
中科院分区:
医学4区
文献类型:
--
作者:
Knudsen, BS;Gmyrek, GA;Woude, GFV

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目标。在动物模型中,活性Met受体酪氨酸激酶的表达会导致肿瘤转移。为了分析Met的表达是否可能与前列腺癌细胞的扩散有关,我们调查了它的表达是否与前列腺特异性抗原的复发相关,以及它的表达是否依赖于转移的部位。应用免疫组织化学方法对90例Gleason总分为6~7的前列腺癌根治术标本和86例骨、淋巴结及软组织转移标本进行Met免疫组织化学染色,并对异质性阳性前列腺癌的Met进行半定量评分。用免疫印迹法检测前列腺癌细胞系中MET蛋白的表达。除2例转移性前列腺癌外,所有转移性前列腺癌和51%的原发前列腺癌均表达Met。此外,骨转移癌组织中Met的表达明显高于淋巴结转移瘤。然而,在Gleason总和为6或7的前列腺癌中,甲硫氨酸不是前列腺特异性抗原复发的预后标志。在前列腺癌细胞系中,Met的表达与雄激素受体的表达呈负相关。Met受体酪氨酸激酶在骨转移中的高表达使Met成为核成像和治疗转移性前列腺癌的有希望的靶点。(C)2002年,爱思唯尔科学公司。
Objectives. Expression of the active Met receptor tyrosine kinase causes tumor metastasis in animal models. To begin to analyze whether Met expression might be related to the spread of prostate cancer cells, we investigated whether its expression correlates with prostate-specific antigen recurrence and whether its expression depends on the site of metastasis.Methods. Ninety radical prostatectomy specimens with a Gleason sum of 6 or 7 and 86 specimens of bone, lymph node, and soft-tissue metastasis were immunohistochemically stained for Met, and a semiquantitative scoring system for Met in heterogeneously positive prostate cancers was applied. Met protein in prostate cancer cell lines was measured by Western blotting.Results. With the exception of two lymph node metastases, all metastases and 51% of the primary prostate cancers expressed Met. Moreover, the bone metastases expressed significantly more Met than did the lymph node metastases. However, in prostate cancer with a Gleason sum of 6 or 7, Met was not a prognostic marker for prostate-specific antigen recurrence. In prostate cancer cell lines, Met expression correlated inversely with expression of the androgen receptor.Conclusions. The high expression of the Met receptor tyrosine kinase in bone metastasis renders Met a promising target for nuclear imaging and treatment of metastatic prostate cancer. (C) 2002, Elsevier Science Inc.