Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yu
Decai
D
Institute of Hepatobiliary Surgery, Nanjing University, Nanjing, Jiangsu Province, PR China. dryudecai@hotmail.com <dryudecai@hotmail.com>
Zhuang
Linyuan
L
Sun
Xitai
X
Chen
Jun
J
Yao
Yongzhong
Y
Meng
Kui
K
Ding
Yitao
Y
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000627:therapeutic use; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A