Table_1_Tenascin-W Is a Novel Stromal Marker in Biliary Tract Cancers.docx

Extrahepatic cancers of the biliary system are typically asymptomatic until after metastasis, which contributes to their poor prognosis. Here we examined intrahepatic cholangiocarcinomas (n = 8), carcinomas of perihilar bile ducts (n = 7), carcinomas of the gallbladder (n = 11) and hepatic metastasis from carcinomas of the gallbladder (n = 4) for the expression of the extracellular matrix glycoproteins tenascin-C and tenascin-W. Anti-tenascin-C and anti-tenascin-W immunoreactivity was found in all biliary tract tumors examined. Unlike tenascin-C, tenascin-W was not detected in normal hepatobiliary tissue. Tenascin-W was also expressed by the cholangiocarcinoma-derived cell line Huh-28. However, co-culture of Huh-28 cells with immortalized bone marrow-derived stromal cells was necessary for the formation and organization of tenascin-W fibrils in vitro. Our results indicate that tenascin-W may be a novel marker of hepatobiliary tumor stroma, and its absence from many normal tissues suggests that it may be a potential target for biotherapies.

胆道系统肝外癌通常在发生转移前无明显临床症状，这也是其预后不佳的重要诱因。本研究针对肝内胆管癌（n=8）、肝门部胆管癌（n=7）、胆囊癌（n=11）及胆囊癌肝转移灶（n=4），检测了细胞外基质糖蛋白腱生蛋白-C（tenascin-C）与腱生蛋白-W（tenascin-W）的表达水平。抗腱生蛋白-C与抗腱生蛋白-W的免疫反应性在所有受试胆道系统肿瘤中均呈阳性。与腱生蛋白-C不同，正常肝胆组织中未检测到腱生蛋白-W的表达。胆管癌细胞系Huh-28同样可表达腱生蛋白-W。但体外实验表明，需将Huh-28细胞与永生化骨髓来源基质细胞共培养，方可形成并有序组装腱生蛋白-W原纤维。本研究结果显示，腱生蛋白-W或可作为肝胆肿瘤间质的新型标志物；其在多数正常组织中缺失这一特性，提示其有望成为生物治疗的潜在靶点。