Shedding of distinct cryptic collagen epitope (HU177) in sera of melanoma patients.
Shedding of distinct cryptic collagen epitope (HU177) in sera of melanoma patients.
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黑色素瘤患者血清中不同隐秘胶原表位（HU177）的脱落。
DOI：
10.1158/1078-0432.ccr-07-4992
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发表时间：
2008-10-01
期刊：
影响因子：
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通讯作者：
Osman I
中科院分区：
文献类型：
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作者：
Ng B;Zakrzewski J;Warycha M;Christos PJ;Bajorin DF;Shapiro RL;Berman RS;Pavlick AC;Polsky D;Mazumdar M;Montgomery A;Liebes L;Brooks PC;Osman I
肿瘤生长过程中细胞外基质重塑在血管生成中起重要作用。我们的临床前数据表明，一个新发现的隐蔽表位（HU 177）内胶原IV型调节内皮细胞和黑色素瘤细胞的粘附在体外和血管生成在体内。在本研究中，我们研究了黑素瘤患者血清中HUI 77脱落的临床相关性。通过新开发的夹心ELISA测定法分析了来自纽约大学医学中心前瞻性招募的291名黑素瘤患者和106名对照受试者的血清样品的HU 177表位浓度。然后将HU 177血清水平与临床和病理参数相关联。平均HU 177表位浓度为5.8 ng/ml（范围=0-139.8 ng/ml）。HU 177浓度与结节性黑色素瘤组织学亚型之间观察到显著相关性（结节性，10.3±1.6ng/ml（平均值±SEM）;浅表扩散性黑色素瘤，4.5± 1.1ng/ml;所有其他，6.1±2.1ng/ml;通过ANOVA检验，P=0.01）。HU 177脱落增加也与肿瘤厚度相关（≤ 1.00 mm，3.8± 1.1 ng/ml; 1.01- 3.99 mm，8.7± 1.3 ng/ml; ≥ 4.00 mm，10.3± 2.4 ng/ml; ANOVA分析P=0.003）。在控制厚度的多变量分析后，较高的HU 177浓度与结节亚型之间的相关性仍然显著（P=0.03）。对照受试者中的平均HU 177表位浓度为2.4ng/ml。我们报告说，原发性黑色素瘤可以诱导可检测的变化，在系统水平的隐蔽表位脱落。我们的数据也支持结节性黑色素瘤可能是生物学上不同的浅表扩散型黑色素瘤相比。由于针对隐蔽胶原蛋白表位的靶向干预目前正在进行I期临床试验测试，这些发现表明结节性黑色素瘤患者可能更容易受到这种靶向治疗的影响。
Extracellular matrix remodelling during tumor growth plays an important role in angiogenesis. Our preclinical data suggest that a newly identified cryptic epitope (HU177) within collagen type-IV regulates endothelial and melanoma cell adhesion in vitro and angiogenesis in vivo. In this study, we investigated the clinical relevance of HUI77 shedding in melanoma patient sera. Serum samples from 291 melanoma patients prospectively enrolled at the New York University Medical Center and 106 control subjects were analyzed for HU177 epitope concentration by a newly-developed sandwich ELISA assay. HU177 serum levels were then correlated with clinical and pathologic parameters. Mean HU177 epitope concentration was 5.8ng/ml (range=0–139.8 ng/ml). A significant correlation was observed between HU177 concentration and nodular melanoma histological subtype (nodular, 10.3±1.6ng/ml (mean ±SEM); superficial spreading melanoma, 4.5±1.1 ng/ml; all others, 6.1±2.1ng/ml; P=0.01 by ANOVA test). Increased HU177 shedding also correlated with tumor thickness (≤1.00mm, 3.8±1.1ng/ml; 1.01–3.99mm, 8.7±1.3ng/ml; ≥4.00mm, 10.3±2.4ng/ml; P=0.003 by ANOVA). After multivariate analysis controlling for thickness, the correlation between higher HU177 concentration and nodular subtype remained significant (P=0.03). The mean HU177 epitope concentration in control subjects was 2.4ng/ml. We report that primary melanoma can induce detectable changes in systemic levels of cryptic epitope shedding. Our data also support that nodular melanoma might be biologically distinct compared to superficial spreading type melanoma. As targeted interventions against cryptic collagen epitopes are currently undergoing phase I clinical trial testing, these findings indicate that patients with nodular melanoma may be more susceptible to such targeted therapies.