Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Oncol Rep. 2017 Nov;38(5):2697-2704. doi: 10.3892/or.2017.5980. Epub 2017 Sep 20.
C4.4A is a glycoprotein that is upregulated in several human malignancies, including colorectal, breast and renal cell carcinomas. Due to its highly restricted expression in healthy tissue, C4.4A was proposed as a potential diagnostic marker. Thus, the present study was designed to evaluate C4.4A expression and function in hepatocellular carcinoma (HCC) for the first time. Immunohistochemistry was performed to detect expression of C4.4A in human sections of healthy liver, primary HCC in the liver and metastatic HCC in the lung. To assess the contribution of C4.4A to HCC progression proliferation, apoptosis, migration and invasion assays were performed with C4.4A knockdown Huh7 and HepG2 cells. C4.4A is absent in healthy liver tissue. However, intense expression was seen in 59% of primary HCCs and strong expression in 80% of HCC lung metastases. C4.4A expression was also observed in human HCC cell lines, which strongly increased under hypoxic conditions. A C4.4A knock-down revealed that C4.4A is involved in both migration and invasion of HCC cells. Taken together, C4.4A expression in both primary and metastatic HCC suggests its potential value as a diagnostic marker for HCC. Due to its absence in healthy liver tissue, C4.4A might even serve as a possible therapeutic target, particularly for metastatic HCC.
C4.4A 是一种糖蛋白，在包括结直肠癌、乳腺癌和肾细胞癌在内的多种人类恶性肿瘤中上调。由于其在健康组织中表达高度受限，C4.4A 被提议作为一种潜在的诊断标志物。因此，本研究首次旨在评估 C4.4A 在肝细胞癌 (HCC) 中的表达和功能。通过免疫组织化学检测人肝组织、肝原发性 HCC 和肺转移性 HCC 中 C4.4A 的表达。为了评估 C4.4A 对 HCC 进展的贡献，进行了 C4.4A 敲低 Huh7 和 HepG2 细胞的增殖、凋亡、迁移和侵袭测定。C4.4A 在健康的肝组织中不存在。然而，在 59%的原发性 HCC 中观察到强烈的表达，在 80%的 HCC 肺转移中观察到强烈的表达。C4.4A 在人类 HCC 细胞系中也有表达，在低氧条件下强烈增加。C4.4A 敲低表明 C4.4A 参与 HCC 细胞的迁移和侵袭。总之，原发性和转移性 HCC 中的 C4.4A 表达表明其作为 HCC 诊断标志物的潜在价值。由于其在健康的肝组织中不存在，C4.4A 甚至可能成为转移性 HCC 的潜在治疗靶点。
