Elevated expression of endoglin, a component of the TGF-?-receptor complex, correlates with proliferation of tumor endothelial cells

Miller, Daniel W.; Graulich, Wolff; Karges, Bernadett; Stahl, Sabine; Ernst, Michael E.; Ramaswamy, Annette; Sedlacek, H.H.; Müller, Rolf; Adamkiewicz, Jürgen

doi:10.1002/(sici)1097-0215(19990517)81:4<568::aid-ijc11>3.0.co;2-x

Cited by 182 publications

(128 citation statements)

References 19 publications

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“…By immunostaining of a variety of tissues, we and others have observed that whereas Mab to CD105 has a high affinity for angiogenic blood vessels (e.g. in tumours, stroke and psoriatic tissues), it often fails to react with the normal microvessels decorated by pan-endothelial markers, for example, CD31, vWF, CD34, PAL-E (Burrows et al, 1995;Kumar et al, 1996;Bodey et al, 1998;Miller et al, 1999;Brewer et al, 2000;Fonsatti et al, 2001 and our unpublished data). These observations demonstrate that CD105 and the pan-endothelial markers are differentially expressed in angiogenic and normal EC, and that the former is more suitable for identifying tumour angiogenesis.…”

Section: Discussionmentioning

confidence: 50%

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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CD105 and its ligand transforming growth factor b (TGFb) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40 -9.00) and 3.10 (range 0.90 -8.00), respectively. Kaplan -Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFb1 and TGFb3 together with the receptor -ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFb1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFb1 level was noted in patients with carcinoma over the controls. Furthermore, TGFb3 and CD105/ TGFb3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFb1 was expressed in cancer cells but TGFb3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFb1, TGFb3 and CD105/TGFb complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

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Section: Discussionmentioning

confidence: 50%

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

et al. 2003

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“…So far, the role of endoglin in angiogenesis has been studied primarily in tumor endothelial cells of various organs [4][5][6][7][8] . A marked increase in the expression of endoglin has been demonstrated on the surface of vascular endothelial cells 9) . A recent study which investigated patients with coronary artery disease suggested that endoglin may be important in the pathogenesis of atherosclerotic disease 10) .…”

Section: Introductionmentioning

confidence: 98%

Significant Expression of Endoglin (CD105), TGFβ-1 and TGFβ R-2 in the Atherosclerotic Aorta: An Immunohistological Study

Piao

Tokunaga

2006

J Atheroscler Thromb

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To date, the glycoprotein endoglin and its receptor complex, formed between TGF and TGF R-2, have been studied in tumor angiogenesis. The purpose of this study is to investigate the expression profile of endoglin and its receptor complex in human atherosclerotic lesions, and compare it to that in non-atherosclerotic tissues. Twenty-six atherosclerotic lesions and twenty-six non-atherosclerotic aortic tissues were collected from thirty-six autopsy cases. Indirect immunohistochemical staining was performed to detect the presence of endoglin, TGF -1, and TGF R-2 proteins in aortic tissues.

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“…CD105 is a homodimeric membrane glycoprotein expressed on endothelial cells that can bind to TGF-1 and -3. It is only expressed on active endothelial cells and consequently be able to reflect a neoangiogenesis in malignant tumors [10,18]. Neovascularization provides not only the route for nutrient supply to the tumor but also the conduit for tumor cells to be shed into the circulation because newly formed vessels are often absent of basement membrane [19].…”

Section: Discussionmentioning

confidence: 99%

Expression of CD105 (Endoglin) in Hepatocellular Carcinoma and Correlation with Intrahepatic Metastasis: Analysis Using Tissue Microarrays and Comparison with Other Endothelial Marker

Lee¹,

Mori²,

Takase³

et al. 2009

TOPATJ

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Neovascularization provides the route for nutrient supply to the tumor and the conduit for tumor cells to be shed into the circulation. CD31 is a pan-endothelial cell marker and CD105 is an active endothelial cell marker, but whether there is a link between CD105 expression and metastasis in Hepatocellular carcinoma (HCC) still remains unclear. A tissue microarray containing 38 HCCs and adjacent non-tumorous liver tissue samples was constructed. The microvessel density (MVD) of CD31, CD105, vWF and the expression of PCNA, VEGF were investigated in a HCC tissue microarray by immunohistochemistry. There was a significant difference between the score of MVD-CD31 in HCC (48.5 ± 29.7) and non-tumorous liver tissue (24.2 ± 22.3, P<0.01). The mean score of MVD-CD31 was higher in HCCs with high PCNA expression (68.4 ± 37.0) than in HCCs with low PCNA expression (37.9 ± 30.9, P = 0.012). MVD-CD105 and VEGF expression were significantly higher in HCC with intrahepatic metastasis (P < 0.01). Multivariate analysis confirmed that MVD-CD105 but not MVD-CD31 was an independent contributing factor to the intrahepatic metastasis. In conlusions, MVD-CD105 expression is associated with intrahepatic metastasis of HCC. Because CD105 is expressed in the activated endothelial cells of the newly formed blood vessels, neovascularization is important in the metastasis of HCC.

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Elevated expression of endoglin, a component of the TGF-?-receptor complex, correlates with proliferation of tumor endothelial cells

Cited by 182 publications

References 19 publications

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Significant Expression of Endoglin (CD105), TGFβ-1 and TGFβ R-2 in the Atherosclerotic Aorta: An Immunohistological Study

Expression of CD105 (Endoglin) in Hepatocellular Carcinoma and Correlation with Intrahepatic Metastasis: Analysis Using Tissue Microarrays and Comparison with Other Endothelial Marker

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Elevated expression of endoglin, a component of the TGF-?-receptor complex, correlates with proliferation of tumor endothelial cells

Cited by 182 publications

References 19 publications

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

Significant Expression of Endoglin (CD105), TGF&beta;-1 and TGF&beta; R-2 in the Atherosclerotic Aorta: An Immunohistological Study

Expression of CD105 (Endoglin) in Hepatocellular Carcinoma and Correlation with Intrahepatic Metastasis: Analysis Using Tissue Microarrays and Comparison with Other Endothelial Marker

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Significant Expression of Endoglin (CD105), TGFβ-1 and TGFβ R-2 in the Atherosclerotic Aorta: An Immunohistological Study