Continuous Endoglin (CD105) Overexpression Disrupts Angiogenesis and Facilitates Tumor Cell Metastasis

Ollauri-Ibáñez, Claudia; Núñez-Gómez, Elena; Egido-Turrión, Cristina; Silva-Sousa, Laura; Rodríguez-Barbero, Alicia; López‐Novoa, José M.; Pericacho, Miguel

doi:10.1101/691824

Cited by 3 publications

(3 citation statements)

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“…Tumor angiogenesis plays a crucial role in the initiation of tumors, and their progression, invasion, and metastasis ( 6 , 7 ). Antiangiogenic therapies represent a promising anticancer treatment strategy, already extensively used for the treatment of solid tumors, aiming to inhibit tumor angiogenesis by targeting the key signaling pathways in which it is implicated ( 8 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis

et al. 2021

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BackgroundPrevious studies, both in vitro and in vivo, have established that apatinib has anti-tumor properties. However, insufficient empirical evidence of the efficacy and safety of apatinib has been published for bone and soft tissue sarcoma, the reported results differing widely. Here, we conducted a meta-analysis to assess the efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma.MethodsPubmed, Medline, Web of Science, ScienceDirect, Ovid, Embase, Cochrane Library, Scopus, Vip (China), Cnki (China), Wanfang (China), and CBM (China) databases and literature from conferences were searched for studies of apatinib for the treatment of bone and soft tissue sarcomas, published from the inception of each database to Sep 1, 2020, without language restrictions. Primary outcomes were efficacy and toxicity of apatinib for the treatment of bone and soft tissue sarcoma, including treatment response, progression-free survival (PFS), and the incidence of adverse events. After extraction of data and methodological quality evaluation, random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using R software (Version 3.4.1).ResultsA total of 21 studies with 827 participants were included in the present meta-analysis. The mean MINORS score was 10.48 ± 1.75 (range: 7-13), indicating evidence of moderate quality. Pooled outcomes indicated that overall response rate (ORR) and disease control rate (DCR) were 23.85% (95% CI: 18.47%-30.21%) and 79.16% (95% CI: 73.78%-83.68%), respectively. Median PFS ranged from 3.5 to 13.1 months, with a mean of 7.08 ± 2.98 months. Furthermore, the rates of PFS (PFR) after 1, 6, and 12 months were 99.31%, 44.90%, and 14.31%, respectively. Drug-related toxicity appears to be common in patients administered apatinib, for which hand-foot syndrome (41.13%), hypertension (36.15%), and fatigue (20.52%) ranked the top three most common adverse events. However, the incidence of grade 3-4 adverse events was relatively low and manageable.ConclusionsBased on the best evidence currently available, apatinib demonstrates promising clinical efficacy and an acceptable safety profile for the treatment of advanced bone and soft tissue sarcoma, although additional high-quality clinical studies are required to further define its properties and toxicity.

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Section: Introductionmentioning

confidence: 99%

Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis

et al. 2021

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“…The first one, CD105 is a well-known receptor for TGF-β [19]. It has been widely researched in the topic of cancer, especially tumour angiogenesis [20]. However, while it is also expressed in stem cells, its role is currently not fully elucidates, as it was demonstrated that its expression has no effect on differentiation ability and does not allow to distinguish a population of MSCs able to progress towards a chondrogenic lineage fate [21].…”

Section: Discussionmentioning

confidence: 99%

qPCR analysis of mesenchymal stem cell marker expression during the long-term culture of canine adipocyte derived stem cells

Bryl

Dompe

Jankowski

et al. 2020

Medical Journal of Cell Biology

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Due to its availability and accessibility, adipose tissue has been the subject of various studies in many different medical fields and is believed to be a useful source of stem cells. The ability of ASCs to differentiate towards different cell lineages, with possibility of directing this differentiation, increases their possible clinical applications, and they have been widely employed in multiple therapies and treatment of different pathologies. However, a deeper understanding of the molecular mechanisms underlying the ASCs osteoblastic and chondrocyte differentiation may lead to novel applications treating a multitude of different bone-related diseases through techniques more likely meeting worldwide consensus. In this study, the RT-qPCR method was used to determine the changes in expression of ASC specific markers (CD105, CD73, CD14, CD34, CD90 and CD45) before and after long-term (14-day) in vitro cultures. To confirm the identity of the investigated cells, flow cytometry was used to evaluate the presence of positive (CD44, CD90) and negative (CD45, CD34) ASC markers. Overall, the results of the PCR analysis showed a significant change in expression of most of the marker genes, indicating significant changes in the cultured cells caused by their long-term culture, potentially altering their original stem-like characteristics.Running title: ASC marker expression during long-term in vitro culture

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“…This autosomal dominant disorder, characterized by abnormal blood vessel formation, illustrates how mutations in endoglin result in clinical manifestations such as epistaxis and arteriovenous malformations (AVMs) in critical organs, posing serious health risks. [4][5][6][7][8][9] Although virtually all endothelial cells in HHT patients suffer from haploinsufficiency, AVMs are rare, suggesting the occurrence of "additional hits" for their manifestation, such as somatic mutation, mechanical trauma and/or inflammation. [10][11][12] This complexity is further illustrated by studies correlating AVMs with decreased endoglin expression and abnormal responses to angiogenic stimuli such as VEGF.…”

Section: Introductionmentioning

confidence: 99%

Endoglin regulates the integrity of the bone marrow vasculature

Rodriguez,

Jaykar,

Watts

et al. 2024

Preprint

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Endoglin (Eng) is an accessory receptor for transforming growth factor-β (TGF-β) that is critical for maintaining vascular integrity. Mutations in Eng cause hereditary hemorrhagic telangiectasia (HHT), resulting in arteriovenous malformations (AVMs) and blood abnormalities. Despite the known association between Eng deficiency and AVMs, the underlying mechanisms are unclear. In addition, the role of the bone marrow (BM), a major source of immune and blood cells, in endothelial Eng (EC-Eng) deficiency is unexplored. We show that BM blood vessels conditionally deficient in Eng (cKO) undergo a structured remodeling process over four weeks, with distinct proliferative and resolution phases. These phases involve angiogenic set points, the involvement of integrins, and the modulation of vascular integrity. In addition, we observe changes in hematopoietic stem and progenitor cells (HSPC) and circulating granulocytes, along with reduced red blood cells and platelets due to splenic sequestration. Using a conditional heterozygous EC-Eng deficient mouse model, reflecting the genetics of HHT patients, we identify vascular changes similar to those in the cKO model. Taken together, using multiple in vivo approaches, we suggest that reduced Eng expression in the endothelium drives significant BM vascular remodeling, sharing mechanisms with early vascular processes associated with AVM formation.

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Continuous Endoglin (CD105) Overexpression Disrupts Angiogenesis and Facilitates Tumor Cell Metastasis

Cited by 3 publications

References 50 publications

Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis

Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis

qPCR analysis of mesenchymal stem cell marker expression during the long-term culture of canine adipocyte derived stem cells

Endoglin regulates the integrity of the bone marrow vasculature

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