Endoglin: Beyond the Endothelium

Schoonderwoerd, Mark J.A.; Goumans, Marie–José; Hawinkels, Lukas J.A.C.

doi:10.3390/biom10020289

Cited by 80 publications

(63 citation statements)

References 149 publications

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“…Although initially studies on endoglin were focused on its role in endothelial cells and angiogenesis, early results provided data that showed endoglin expression on macrophages [ 11 ], leukocytes, syncytiotrophoblasts in the placenta [ 12 ] and fibroblasts in culture [ 13 ]. More recent work has revealed a crucial role for endoglin expression on other non-endothelial cells, which we have recently reviewed [ 14 ]. In both endothelial and non-endothelial cells, endoglin regulates TGF-β family member signaling.…”

Section: Introductionmentioning

confidence: 99%

Endoglin Targeting: Lessons Learned and Questions That Remain

Liu

Paauwe

Nixon

et al. 2020

IJMS

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Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.

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Section: Introductionmentioning

confidence: 99%

Endoglin Targeting: Lessons Learned and Questions That Remain

Liu

Paauwe

Nixon

et al. 2020

IJMS

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“…Interestingly, soluble endoglin is a circulating cleaved form of membrane endoglin, a transmembrane glycoprotein related to the function of vascular endothelium [ 18 ]. Soluble endoglin might represent an interesting biomarker of increased cholesterol levels since it was shown to be elevated in hypercholesterolemic [ 19 ] and FH patients [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients

Víšek

Bláha

et al. 2021

Orphanet J Rare Dis

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Background Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. Results 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. Conclusions LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

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“…CD105 is a homodimeric transmembrane glycoprotein, and an auxiliary receptor of transforming growth factor-β (TGF-β), which binds to TGF-β1 and TGF-β3. It modulates TGF-β signaling by interacting with type I and type II TGF-β receptors, and activates a complex signaling pathway involving endothelial cell proliferation, migration and adhesion [10][11][12]. A recent meta-analysis on 30 studies involving 3,613 cancer patients found strong evidence of an increased CD105 expression in tumor microvessels correlating with poor overall survival, disease-free survival (DFS), and cancer-specific survival rates [10].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of CD105- and CD31-Assessed Microvessel Density in Paired Biopsies and Surgical Samples of Laryngeal Carcinoma

Marioni

Franz

Ottaviano

et al. 2020

Cancers

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Small pretreatment laryngeal biopsies may not fully represent a tumor’s biological profile. This study on laryngeal squamous cell carcinoma (LSCC) aimed to investigate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in paired biopsies and surgical specimens and the association and discrepancy between CD105- and CD31-assessed MVD in biopsies and surgical specimens. CD105- and CD31-assessed MVD was analyzed in paired biopsies and surgical specimens of 45 consecutive cases of LSCC. In the LSCC biopsies and surgical specimens, median CD105-assessed MVD was significantly higher in N+ than in N0 cases (p = 0.0008, and p = 0.0002, respectively). Disease-free survival (DFS) was associated with CD105- and CD31-assessed MVD in both biopsies and surgical specimens (p < 0.0001 for all specimens). Multivariable Cox’s regression showed that pathological grade (p < 0.0001) and CD105-assessed MVD in LSCC biopsies (p = 0.0209) predicted DFS. Lin’s concordance coefficient showed that CD31 overestimated MVD compared with CD105 in LSCC biopsies and surgical specimens. CD105-assessed MVD should be further investigated in larger LSCC series as a potential prognostic marker for identifying: patients at higher risk of recurrence who might warrant more aggressive therapy; and cN0 patients requiring elective neck dissection for a significant risk of regional metastasis.

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Endoglin: Beyond the Endothelium

Abstract: Keywords: endoglin; CD105 TGF-β; BMP9; ALK-1; TRC105; tumor microenvironment

Cited by 80 publications

References 149 publications

Endoglin Targeting: Lessons Learned and Questions That Remain

Endoglin Targeting: Lessons Learned and Questions That Remain

Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients

Prognostic Significance of CD105- and CD31-Assessed Microvessel Density in Paired Biopsies and Surgical Samples of Laryngeal Carcinoma

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