Synergy between anti‐endoglin (CD105) monoclonal antibodies and TGF‐β in suppression of growth of human endothelial cells

She, Xinwei; Matsuno, Fumihiko; Harada, Naoko; Tsai, Hilda; Seon, Ben K.

doi:10.1002/ijc.11551

Cited by 63 publications

(48 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These effects are potentially inhibited by a dual blockade of the TGF-β and CD105 pathways (35). Moreover, the anti-CD105 antibody as a single agent as well as CD105 as a target for an oral DNA vaccine have also been reported to be effective agents for suppressing or preventing tumor progression and prolonging survival in in vitro models (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers

Rau

Huang

Chiu

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Angiogenesis is critical for the growth, invasion and metastasis of cancers. Extensive neovascularization and tumor thrombus also correlate with a poor prognosis in breast cancer (BC). Although anti-angiogenic agents have been the therapies of choice for BC, in particular for triple-negative BCs, predictive markers for anti-angiogenic agents are lacking. Microvascular density (MVD) is commonly used to assess the neovascularization in tumors. Compared with pan-endothelial markers such as CD31, CD34 and von Willebrand factor (vWF), CD105 has a higher specificity for MVD in tumor tissues. In this study, we aimed to determine the prognostic value of CD105 in BCs. Paraffin-embedded tissue blocks from 201 BC patients were formed into tissue microarrays. Evaluation of MVD revealed that a median of 11 microvessels determined by CD105 staining correlated significantly with the pathological characteristics of BCs and also with the survival of patients. The expression of CD105 correlated inversely with hormone receptor (HR) expression but positively with Her-2 expression. Univariate analysis indicated that CD105 is a superior predictor of disease-free survival (DFS) in stage I and II diseases; multivariate analysis indicated that only hormone receptors (HRs) are suitable for predicting overall survival (OS) in stage III disease. These findings reveal for the first time that MVD measured by CD105 staining correlates positively with Her-2 expression but negatively with HR expression. The significance of MVD on OS is more apparent in early stage BCs. CD105 has the potential to be used as a predictive marker for anti-angiogenic agents; the targeting of CD105 may also be a potential anticancer strategy.

show abstract

Section: Discussionmentioning

confidence: 99%

Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers

Rau

Huang

Chiu

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Therefore, a proliferation-associated antigen on endothelial cells may be a good candidate for anti-angiogenic therapy. Endoglin has been proven to be a proliferationassociated antigen on endothelial cells [7,31,32] . Previous studies demonstrated that anti-endoglin mAbs showed a highly restricted reactivity to proliferating endothelial cells, immature acute lymphoblastic leukemia (ALL) cells and myeloid/monocytic leukemia cells [4,33,34] .…”

Section: Discussionmentioning

confidence: 99%

“…Studies performed in different laboratories using various antibodies to endoglin have revealed endoglin expression and upregulation in a wide range of tumor endothelia, but seldom found in the endothelia of normal tissues, suggesting that endoglin is highly related to tumor angiogenesis [5,6] . In addition, another study demonstrated that blockage of the endoglin pathway in human umbilical vein endothelial cells resulted in marked a inhibition of in vitro angiogenesis in combination with TGF-β, indicating that endoglin is a pro-angiogenic component in the endothelial cells [7] . Therefore, therapeutic approach targeting endoglin may potentially have the capability of avoiding system sideeffects.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

Tan¹

2007

WJG

View full text Add to dashboard Cite

AIM:To explore the capability of a monoclonal antibody (mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models. METHODS:A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay. RESULTS:Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice. Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with antiendoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb. CONCLUSION:Passive immunotherapy with antiendoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

show abstract

“…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]. Recent research has shown that CD105 is only weakly expressed in normal tissues, but it is strongly expressed in tumor endothelial cells [10,20,21]. CD105 has been demonstrated to be a good tumor angiogenesis marker in breast cancer [22], colorectal cancer [10,23] and melanoma [24].…”

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

View full text Add to dashboard Cite

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.

show abstract

Synergy between anti‐endoglin (CD105) monoclonal antibodies and TGF‐β in suppression of growth of human endothelial cells

Cited by 63 publications

References 34 publications

Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers

Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers

Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

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

Contact Info

Product

Resources

About