Article
Biochemistry & Molecular Biology
V. B. Sameer Kumar, K. Anjali
Summary: One of the major reasons for the non-effectiveness of anticancer therapeutics targeting tumour angiogenesis is the complexity of cellular communication in the tumour micro-environment. Recent research has highlighted the importance of signaling events mediated by exosomes in tumor progression and angiogenesis. This review collates information on the role of exosomal cargo, especially exosomal miRNAs, in modulating tumor angiogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Letter
Peripheral Vascular Disease
Yara Onetti, Roland E. Kaelin, Bettina Pitter, Mengzhuo Hou, Victor Arribas, Rainer Glass, Eloi Montanez
Summary: Endothelial alpha-pv is necessary for tumor angiogenesis and progression. Using an inducible knockout approach, researchers found that loss of endothelial alpha-pv reduces vessel density and vascular complexity in the pathological neo-vasculature of brain tumor-bearing mice. This reduction in tumor vascularization is associated with increased tumor cell apoptosis and decreased tumor volume.
Article
Multidisciplinary Sciences
Wen Luo, Irene Garcia-Gonzalez, Macarena Fernandez-Chacon, Veronica Casquero-Garcia, Maria S. Sanchez-Munoz, Severin Muhleder, Lourdes Garcia-Ortega, Jorge Andrade, Michael Potente, Rui Benedito
Summary: The formation of arteries is not directly induced by a Notch-dependent arterial differentiation program, but depends on the timely suppression of endothelial cell-cycle progression and metabolism.
Article
Peripheral Vascular Disease
Timothy Sargis, Seock-Won Youn, Krishna Thakkar, L. A. Naiche, Na Yoon Paik, Kostandin Pajcini, Jan K. Kitajewski
Summary: The Notch signaling pathway is an important therapeutic target for inflammatory diseases and cancer. Researchers have optimized the design of Notch inhibitors and created highly secreted Notch antibodies, which have been proven to have anti-angiogenic properties.
Review
Biochemistry & Molecular Biology
Selvaraj Vimalraj
Summary: Angiogenesis is the formation of new blood vessels from existing ones. Abnormal angiogenesis, seen in tumor microenvironments, is characterized by distorted and leaky blood vessels with various shapes and high perfusion efficiency. Tumor angiogenesis plays a crucial role in cancer growth, invasion, and metastasis, and is tightly regulated by signaling networks. Targeting multiple signaling pathways involved in angiogenesis is important for effective antiangiogenic therapy. New therapeutic approaches, such as blocking specific proteins or genes, are being explored to dissect alternative angiogenesis mechanisms in tumor microenvironments.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Surgery
Haihong Zhang, Ting Wei, Adam Johnson, Ravi Sun, Gresham Richter, Graham M. Strub
Summary: The study characterized the role of NOTCH signaling cascade activation in the angiogenic drive of infantile hemangioma tissue. The results showed that perturbations in NOTCH signaling follow the natural course and treatment outcome of infantile hemangiomas, suggesting a critical role in their pathogenesis.
JOURNAL OF VASCULAR SURGERY-VENOUS AND LYMPHATIC DISORDERS
(2021)
Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Article
Biochemistry & Molecular Biology
Sara Al-Ghadban, Samantha G. Walczak, Spencer U. Isern, Elizabeth C. Martin, Karen L. Herbst, Bruce A. Bunnell
Summary: This study aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. The impacts of conditioned media (CM) from healthy and lipedema adipocytes on the expression levels of multiple endothelial and angiogenic markers in HUVECs were investigated. The results indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Xiaohua Lu, Lara Johanna Friedrich, Thomas Efferth
Summary: This review comprehensively reports on the current status of natural products against tumor angiogenesis, including their role in anti-angiogenic therapy, types of natural agents, and future perspectives. The review aims to improve the understanding of using natural products for drug development in inhibiting tumor angiogenesis and facilitate the transition of these outcomes into clinical trials.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Peripheral Vascular Disease
Delphine M. Lees, Louise E. Reynolds, Ana Rita Pedrosa, Marina Roy-Luzarraga, Kairbaan M. Hodivala-Dilke
Summary: This study identifies the role of pericyte FAK-Y861 in the regulation of tumor vessel regression and tumor growth control, as well as a dual role in controlling pericyte-derived signals that influence apoptosis in cancer cells. Non-phosphorylatable FAK-Y861F in pericytes reduces tumor growth and blood vessel density.
Article
Medicine, Research & Experimental
Wenyan Fu, Guangyao Li, Changhai Lei, Kewen Qian, Shuyi Zhang, Jian Zhao, Shi Hu
Summary: PARP inhibitors are used in treating BRCA-mutant cancers. Combining bispecific antibodies targeting both EGFR and Notch signalling can decrease the enrichment of stem-like cells, delay the development of acquired resistance, and have a more substantial antitumour effect.
Review
Immunology
Fang Zhao, Yini He, Zhihao Zhao, Jiarong He, Hong Huang, Kelong Ai, Liang Liu, Xiong Cai
Summary: This review discusses the role of Notch signaling in rheumatoid arthritis (RA) and its relationship with angiogenesis. It also explores potential strategies targeting the Notch signaling to improve the treatment outcomes of RA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Qian Xie, Huiling Guo, Peirong He, Huan Deng, Yanjun Gao, Ningning Dong, Wenbo Niu, Tiancai Liu, Ming Li, Suihai Wang, Yingsong Wu, Ji-Liang Li
Summary: High expression of Tspan5 is significantly associated with clinicopathological features and poor survival in HCC patients, promoting cell migration and tumour metastasis. Mechanistically, Tspan5 enhances ADAM10 enzymatic activity, activates Notch signaling, and induces epithelial-mesenchymal transition in tumour cells. These findings highlight the pivotal role of Tspan5 in regulating Notch signaling, EMT, and tumour metastasis in HCC.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Hongyuan Lu, Cen Wu, Xiao-wen Jiang, Qingchun Zhao
Summary: This study found that the ADAM-17 inhibitor ZLDI-8 significantly inhibits angiogenesis and vasculogenic mimicry (VM) in drug-resistant NSCLC by suppressing the Notch1-HIF1αVEGF signaling pathway. This study lays the foundation for the discovery of drugs that inhibit angiogenesis and VM in drug-resistant NSCLC.
Article
Oncology
Mary E. Vail, Rae H. Farnsworth, Linda Hii, Stacey Allen, Sakshi Arora, Robin L. Anderson, Ross A. Dickins, Akira Orimo, Sunny Z. Wu, Alexander Swarbrick, Andrew M. Scott, Peter W. Janes
Summary: We have identified the cell guidance receptor EphA3 on distinct stromal/fibroblast-like cell types in the tumour microenvironment (TME) that promote growth and angiogenesis. Knockdown of EphA3 expression in the TME reduced mesenchymal stromal/fibroblast-like cells in tumours, with corresponding reductions in tumour vasculature and tumour growth, and increased immune infiltrate. Our results highlight the potential of EphA3 as a therapeutic target for tumour angiogenesis and tumour growth.
Review
Biochemistry & Molecular Biology
Tim Schumertl, Juliane Lokau, Stefan Rose-John, Christoph Garbers
Summary: Interleukin-6 (IL-6) is a pleiotropic cytokine involved in various physiological and pathophysiological functions. It can signal through different pathways, with trans-signaling playing a crucial role in its pro-inflammatory properties. The soluble form of the IL-6 receptor (sIL-6R) is generated by different mechanisms, including proteolysis. Attempts to selectively block IL-6 trans-signaling are being made in pre-clinical animal models and clinical studies for inflammatory bowel disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Neele Schumacher, Stefan Rose-John
Summary: ADAM17 is a metalloprotease responsible for cleaving membrane proteins into soluble proteins, thereby playing a central role in various signaling pathways, particularly in inflammation and carcinogenesis. Its critical functions in IL-6, TNF alpha and EGF-R pathways make it an attractive target for therapeutic interventions, although specific blockade of ADAM17 poses challenges due to its structural homology with other proteases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Stefan Rose-John
Summary: Interleukin-6 is an inflammatory cytokine whose level is elevated in inflammatory states, triggering cell-specific responses. The activation of gp130 in hepatocytes produces both liver-specific and systemic effects.
Article
Cell Biology
Michael Dudek, Kerstin Lohr, Sainitin Donakonda, Tobias Baumann, Max Lu, Silke Hegenbarth, Lena Duebbel, Carola Eberhagen, Savvoula Michailidou, Abdallah Yassin, Marco Prinz, Bastian Popper, Stefan Rose-John, Hans Zischka, Percy A. Knolle
Summary: This study reveals distinct immunometabolic features of liver sinusoidal endothelial cells (LSECs) and LSEC-primed CD8 T cells compared with immunogenic dendritic cells and effector CD8 T cells, highlighting the local metabolism and function of T cells in the liver.
Article
Cell Biology
Alice Prieto Huarcaya, Susy Drobny, Andre R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert, Denise Balta, Christian Werner, Tania Rizo, Lisa Gallwitz, Simon Bub, Iva Stojkovska, Nandkishore R. Belur, Jens Fogh, Joseph R. Mazzulli, Wei Xiang, Amitkumar Fulzele, Mario Dejung, Markus Sauer, Beate Winner, Stefan Rose-John, Philipp Arnold, Paul Saftig, Friederike Zunke
Summary: This study suggests that enhancing SNCA degradation through the application of rHsCTSD can reduce SNCA aggregates in the brains of PD patients and restore endo-lysosome and autophagy function.
Editorial Material
Biochemistry & Molecular Biology
Andreas Herrlich, Eirini Kefaloyianni, Stefan Rose-John
Article
Biochemistry & Molecular Biology
Sophia Kirschke, Ireti Ogunsulire, Balachandar Selvakumar, Neele Schumacher, Tanya Sezin, Stefan Rose-John, Alexander Scheffold, Christoph Garbers, Juliane Lokau
Summary: The cytokine IL-2 plays a crucial role in immune homeostasis. This study demonstrates that metalloproteases ADAM10 and ADAM17 can cleave the IL-2R alpha, generating a soluble ectodomain that inhibits IL-2 signaling in T cells. Manipulating the cleavage of IL-2R alpha offers a potential opportunity to alter IL-2 function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Torben Mentrup, Anna Yamina Stumpff-Niggemann, Nadja Leinung, Christine Schlosser, Katja Schubert, Rebekka Wehner, Antje Tunger, Valentin Schatz, Patrick Neubert, Ann-Christine Gradtke, Janina Wolf, Stefan Rose-John, Paul Saftig, Alexander Dalpke, Jonathan Jantsch, Marc Schmitz, Regina Fluhrer, Ilse D. Jacobsen, Bernd Schroeder
Summary: Dectin-1 plays a critical role in recognizing fungal pathogens through pattern recognition receptors on immune cells. Activation of Dectin-1a results in the formation of a stable receptor fragment lacking the ligand binding domain, which contributes to signal transduction in phagosomal membranes and is terminated by intramembrane proteases SPPL2a and 2b.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Miryam Mueller, Claire Saunders, Anke Senftleben, Johannes P. W. Heidbuechel, Birgit Halwachs, Julia Bolik, Nina Hedemann, Christian Roeder, Dirk Bauerschlag, Stefan Rose-John, Dirk Schmidt-Arras
Summary: Tspan8 subfamily members regulate the substrate selectivity of ADAM17 through different strategies, especially by recruiting ADAM17 into Tspan-enriched micro-domains to promote ADAM17-mediated TNF alpha release. This finding reveals the mechanism of Tspan8's involvement in tumorigenesis.
Article
Immunology
Aikaterini Gatsiou, Simon Tual-Chalot, Matteo Napoli, Almudena Ortega-Gomez, Tommy Regen, Rachit Badolia, Valeriana Cesarini, Claudia Garcia-Gonzalez, Raphael Chevre, Giorgia Ciliberti, Carlos Silvestre-Roig, Maurizio Martini, Jedrzej Hoffmann, Rana Hamouche, Joseph R. Visker, Nikolaos Diakos, Astrid Wietelmann, Domenico Alessandro Silvestris, Georgio Georgiopoulos, Ali Moshfegh, Andre Schneider, Wei Chan, Stefan Guenther, Johanne Backs, Shin Kwak, Craig H. Selzman, Kimon Stamatelopoulos, Stefan Rose-John, Christian Trautwein, Ioakim Spyridopoulos, Thomas Braun, Ari Waisman, Angela Gallo, Stavros G. Drakos, Stefanie Dimmeler, Markus Sperandio, Oliver Soehnlein, Konstantinos Stellos
Summary: RNA editor ADAR2 regulates endothelial responses to IL-6, controlling leukocyte trafficking in inflamed and ischemic tissues. ADAR2 is required for IL-6 trans-signaling and immune cell infiltration through suppressing primary microRNA processing.
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Immunology
Agatha Schwarz, Rebecca Philippsen, Serena G. Piticchio, Jan N. Hartmann, Robert Haesler, Stefan Rose-John, Thomas Schwarz
Summary: The organ-specific microbiome, particularly the skin microbiome, plays a crucial role in tissue homeostasis by regulating the inflammatory response. Short chain fatty acids (SCFA) induce regulatory T cells (Treg) in the skin and their signal is mediated by the receptor HCA2. Knock-out of HCA2 results in stronger inflammation and a switch of Treg from a suppressive to a proinflammatory type, indicating that the skin microbiome dictates the outcome of the inflammatory reaction.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Stefan Rose-John, Brendan J. Jenkins, Christoph Garbers, Jens M. Moll, Juergen Scheller
Summary: This review discusses the discovery of the IL-6 trans-signalling pathway and the development of biologics that specifically inhibit this pathway. Targeting IL-6 trans-signalling can decrease disease-promoting activities of IL-6 without blocking its protective actions.
NATURE REVIEWS IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
P. Bradtke, J. Roesch, D. Reimers, K. Yan, S. Rose-John, H. -W. Mittruecker
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yo Seph Park, Yukyeong Lee, Na Young Choi, Han Sung Hwang, Stefan Rose-John, Martin Zenke, Kinarm Ko
Summary: Umbilical cord blood is an alternative source of hematopoietic stem cells for transplantation, but the low number of HSCs in cord blood is a limitation. This study found that the combination of HIL-6, SR1, and UM171 had a synergistic effect on expanding UCB-HSCs. Therefore, this combination is the best choice for obtaining HSCs for clinical transplantation.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2022)