Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors
Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors
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DOI：
10.1186/1472-6890-12-14
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Chiquet-Ehrismann, Ruth
中科院分区：
文献类型：
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作者：
Brellier, Florence;Martina, Enrico;Chiquet-Ehrismann, Ruth
背景：腱生蛋白是存在于许多胚胎和成人组织的细胞外基质中的大的糖蛋白。生腱蛋白-C是一种研究充分的生物标志物，以其在大多数实体癌的基质中的高过表达而闻名。腱生蛋白-W是该家族中研究最少的成员，在结肠和乳腺肿瘤的间质以及神经胶质瘤中高度表达，但在相应的正常组织中不表达。尚未分析其他实体瘤。本研究旨在确定腱生蛋白-W是否可以作为广泛的实体瘤中的癌症特异性细胞外基质蛋白。方法：我们通过免疫印迹和免疫组织化学分析了胰腺癌、肾癌和肺癌以及黑色素瘤的多个冷冻组织微阵列上的腱生蛋白-W和腱生蛋白-C的表达，并将其与健康组织进行比较。结果：从所有测试的健康成人器官中，仅肝脏和脾脏显示出可检测水平的生腱蛋白-W，表明生腱蛋白-W在正常、非病理条件下不存在于大多数人成人器官中。相比之下，生肿蛋白-W在大多数黑色素瘤及其转移瘤以及胰腺癌、肾癌和肺癌中可检测到。比较每个患者的肺肿瘤样品和匹配的对照组织，揭示了肿瘤组织中生腱蛋白-W的明显过表达。虽然检查的样本数量太少，无法得出统计学上显著的结论，但在更高级别的肿瘤中，似乎存在腱生蛋白-W表达增加的趋势。有趣的是，在大多数肿瘤类型中，腱生蛋白-W也表达在接近血管，如所示的CD31共染色的samples.Conclusions：本研究扩展了肿瘤生物标志物的潜力，腱生蛋白-W广泛的实体瘤，并显示其访问从血流的潜在治疗策略。
Background: Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors.Methods: We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues.Results: From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples.Conclusions: The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.