Yu Decai, Zhuang Linyuan, Sun Xitai, Chen Jun, Yao Yongzhong, Meng Kui, Ding Yitao
Institute of Hepatobiliary Surgery, Nanjing University, Nanjing, Jiangsu Province, PR China.
BMC Cancer. 2007 Jul 4;7:122. doi: 10.1186/1471-2407-7-122.
Endoglin (CD105) has been considered a prognostic marker for hepatocellular carcinoma (HCC), and widely used as an appropriate targeting for antiangenesis therapy in some cancers. Our aim was to evaluate the distribution and expression of CD105 in the liver of patients with HCC, and to discuss whether CD105 may be used as an appropriate targeting for antiangenesis therapy in HCC.
Three parts of liver tissues from each of 64 patients with HCC were collected: tumor tissues (TT), adjacent non-tumor (AT) liver tissues within 2 cm, and tumor free tissues (TF) 5 cm far from the tumor edge. Liver samples from 8 patients without liver diseases served as healthy controls (HC). The distribution and expression of CD105 in tissues were evaluated by immunohistochemistry, Western blotting analysis, and real-time PCR. HIF-1alpha and VEGF165 protein levels in tissues were analyzed by Immunohistochemistry and Western blotting analysis or ELISA.
CD105 was positively stained mostly in a subset of microvessels 'endothelial sprouts' in TT of all patients while CD105 showed diffuse positive staining, predominantly on hepatic sinus endothelial cells in the surrounding of draining veins in TF and AT. The mean score of MVD-CD105 (mean +/- SD/0.74 mm2) was 19.00 +/- 9.08 in HC, 153.12 +/- 53.26 in TF, 191.12 +/- 59.17 in AT, and 85.43 +/- 44.71 in TT, respectively. Using a paired t test, the expression of CD105 in AT and TF was higher than in TT at protein (MVD, p = 0.012 and p = 0.007, respectively) and mRNA levels (p < 0.001 and p = 0.009, respectively). Moreover, distribution and expression of CD105 protein were consistent with those of HIF-1alpha and VEGF165 protein in liver of patients with HCC. The level of CD105 mRNA correlated with VEGF165 level in TF (r = 0.790, p = 0.002), AT (r = 0.723, p < 0.001), and TT (r = 0.473, p = 0.048), respectively.
It is demonstrated that CD105 was not only present in neovessels in tumor tissues, but also more abundant in hepatic sinus endothelium in non-tumor tissues with cirrhosis. Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.
内皮糖蛋白（CD105）被认为是肝细胞癌（HCC）的预后标志物，并在某些癌症中广泛用作抗血管生成治疗的合适靶点。我们的目的是评估CD105在HCC患者肝脏中的分布和表达，并探讨CD105是否可作为HCC抗血管生成治疗的合适靶点。
收集64例HCC患者的三部分肝脏组织：肿瘤组织（TT）、距肿瘤边缘2 cm内的相邻非肿瘤（AT）肝脏组织以及距肿瘤边缘5 cm的无肿瘤组织（TF）。8例无肝脏疾病患者的肝脏样本作为健康对照（HC）。通过免疫组织化学、蛋白质印迹分析和实时PCR评估组织中CD105的分布和表达。通过免疫组织化学、蛋白质印迹分析或ELISA分析组织中HIF-1α和VEGF165蛋白水平。
所有患者的TT中，CD105主要在一部分微血管“内皮芽”中呈阳性染色，而CD105在TF和AT中呈弥漫性阳性染色，主要位于引流静脉周围的肝窦内皮细胞上。HC中MVD-CD105的平均得分（平均值±标准差/0.74 mm2）分别为19.00±9.08，TF中为153.12±53.26，AT中为191.12±59.17，TT中为85.43±44.71。采用配对t检验，AT和TF中CD105的蛋白表达（MVD，p分别为0.012和0.007）和mRNA水平（p分别<0.001和0.009）均高于TT。此外，HCC患者肝脏中CD105蛋白的分布和表达与HIF-1α和VEGF165蛋白的分布和表达一致。TF（r = 0.790，p = 0.002）、AT（r = 0.723，p <0.001）和TT（r = 0.473，p = 0.048）中CD105 mRNA水平分别与VEGF165水平相关。
结果表明，CD105不仅存在于肿瘤组织的新生血管中，而且在伴有肝硬化的非肿瘤组织的肝窦内皮中更丰富。因此，CD105可能不是HCC抗血管生成治疗的合适靶点，尤其是对于伴有肝硬化的患者。
