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

Yu D, Zhuang L, Sun X, Chen J, Yao Y, Meng K, Ding Y - BMC Cancer (2007)

Bottom Line: 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.Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hepatobiliary Surgery, Nanjing University, Nanjing, Jiangsu Province, PR China. dryudecai@hotmail.com <dryudecai@hotmail.com>

ABSTRACT

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.

Conclusion: 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.

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Relative level of VEGF in normal, non-tumor (TF and AT), and tumor tissues and the correlation of VEGF and CD105. A, Relative level of VEGF in HC (n = 8), TF, AT, and TT (n = 36, * p < 0.05 versus HC; # p < 0.05 versus TT). Columns, mean; bars, SD. B, Correlation between VEGF and CD105 mRNA in TF, AT, and TT (n = 36).
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Figure 6: Relative level of VEGF in normal, non-tumor (TF and AT), and tumor tissues and the correlation of VEGF and CD105. A, Relative level of VEGF in HC (n = 8), TF, AT, and TT (n = 36, * p < 0.05 versus HC; # p < 0.05 versus TT). Columns, mean; bars, SD. B, Correlation between VEGF and CD105 mRNA in TF, AT, and TT (n = 36).

Mentions: Previous clinical investigations reported that CD105 correlated with VEGF165 in some tumors, such as non-small cell lung cancer [5], HCC [25], and breast cancer [26]. The distribution and expression of VEGF165 in liver tissues with HCC were evaluated by Immunohistochemistry and ELISA. The positive staining of VEGF165 mainly existed in cytoplasm of tumor cells and hepatocytes (Figure 5B–D). In general, the intensity of VEGF165 staining in the non-tumor tissues (TF and AT) was higher than in tumor tissues (Figure 5C). VEGF165 signals were also present in endothelial cells (Figure 5D). Among the 64 paired specimens, VEGF165 was positively stained in 37.12% of TT, which was lower than in AT (56.23%) and TF (47.91%), but was higher than in normal hepatic tissues (zero, Figure 5A). In addition, ELISA analysis also revealed that VEGF165 protein in HC was significantly lower than in TF, AT, and TT (One-Way ANOVA, p = 0.017). Paired t test showed that VEGF165 protein in TF and AT was significantly higher than in TT (n = 36, p = 0.025, and p = 0.024, respectively; Figure 6A). Paired correlation analysis showed that CD105 mRNA correlated with VEGF165 in TF (r = 0.790, p = 0.002), AT (r = 0.723, p < 0.001), and TT (r = 0.473, p = 0.048), respectively (Figure 6B).


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

Yu D, Zhuang L, Sun X, Chen J, Yao Y, Meng K, Ding Y - BMC Cancer (2007)

Relative level of VEGF in normal, non-tumor (TF and AT), and tumor tissues and the correlation of VEGF and CD105. A, Relative level of VEGF in HC (n = 8), TF, AT, and TT (n = 36, * p < 0.05 versus HC; # p < 0.05 versus TT). Columns, mean; bars, SD. B, Correlation between VEGF and CD105 mRNA in TF, AT, and TT (n = 36).
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Figure 6: Relative level of VEGF in normal, non-tumor (TF and AT), and tumor tissues and the correlation of VEGF and CD105. A, Relative level of VEGF in HC (n = 8), TF, AT, and TT (n = 36, * p < 0.05 versus HC; # p < 0.05 versus TT). Columns, mean; bars, SD. B, Correlation between VEGF and CD105 mRNA in TF, AT, and TT (n = 36).
Mentions: Previous clinical investigations reported that CD105 correlated with VEGF165 in some tumors, such as non-small cell lung cancer [5], HCC [25], and breast cancer [26]. The distribution and expression of VEGF165 in liver tissues with HCC were evaluated by Immunohistochemistry and ELISA. The positive staining of VEGF165 mainly existed in cytoplasm of tumor cells and hepatocytes (Figure 5B–D). In general, the intensity of VEGF165 staining in the non-tumor tissues (TF and AT) was higher than in tumor tissues (Figure 5C). VEGF165 signals were also present in endothelial cells (Figure 5D). Among the 64 paired specimens, VEGF165 was positively stained in 37.12% of TT, which was lower than in AT (56.23%) and TF (47.91%), but was higher than in normal hepatic tissues (zero, Figure 5A). In addition, ELISA analysis also revealed that VEGF165 protein in HC was significantly lower than in TF, AT, and TT (One-Way ANOVA, p = 0.017). Paired t test showed that VEGF165 protein in TF and AT was significantly higher than in TT (n = 36, p = 0.025, and p = 0.024, respectively; Figure 6A). Paired correlation analysis showed that CD105 mRNA correlated with VEGF165 in TF (r = 0.790, p = 0.002), AT (r = 0.723, p < 0.001), and TT (r = 0.473, p = 0.048), respectively (Figure 6B).

Bottom Line: 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.Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hepatobiliary Surgery, Nanjing University, Nanjing, Jiangsu Province, PR China. dryudecai@hotmail.com <dryudecai@hotmail.com>

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus