A5054606212- Angiogenesis and VEGF in Cancer
- Lipid metabolism and disorders
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Cancer Cells and Metastasis
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Hippo pathway signaling and YAP/TAZ
- Cell Image Analysis Techniques
- Cancer Research and Treatments
- Organ Transplantation Techniques and Outcomes
- Axon Guidance and Neuronal Signaling
- Clusterin in disease pathology
- Histone Deacetylase Inhibitors Research
- Bladder and Urothelial Cancer Treatments
- Single-cell and spatial transcriptomics
- Microbial Inactivation Methods
- Liver physiology and pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Virus-based gene therapy research
- Polyamine Metabolism and Applications
- Cellular Mechanics and Interactions
- Peptidase Inhibition and Analysis
- Biomarkers in Disease Mechanisms
Heidelberg University
2015-2025
University Hospital Heidelberg
2020-2025
DKFZ-ZMBH Alliance
2015-2025
German Cancer Research Center
2015-2025
University Medical Centre Mannheim
2024-2025
Abstract The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through supposed endothelial-specific expression. Yet, is also expressed at lower levels by pericytes it has not been unravelled which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human murine express functional receptor. Silencing in results a pro-migratory phenotype. Pericyte controls sprouting vitro vivo...
A temporal systems biology screen of premetastatic endothelial cells identified LRG1 as a therapeutic target for restricting metastases.
// Vignesh Sundararajan 1, 2, 3, * , Nicolas Gengenbacher 4, Marc P. Stemmler 5 Julia A. Kleemann Thomas Brabletz Simone 1 Department of Visceral Surgery, University Medical Center Freiburg, Germany 2 Spemann Graduate School Biology and Medicine (SGBM), Albert-Ludwigs-University 3 Faculty Biology, 4 Division Vascular Oncology Metastasis, German Cancer Research (DKFZ-ZMBH Alliance), Heidelberg, Experimental I, Nikolaus-Fiebiger-Center for Molecular Medicine, Erlangen-Nürnberg, Erlangen,...
Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing regeneration vasculature irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis livers with intact endothelium was solely mediated by proliferation resident ECs. However, following irradiation-induced EC damage, marrow–derived mononuclear...
Abstract The angiopoietin (Angpt)–TIE signaling pathway controls vascular maturation and maintains the quiescent phenotype of resting vasculature. contextual agonistic antagonistic Tie2 ligand ANGPT2 is believed to be exclusively produced by endothelial cells, disrupting constitutive ANGPT1–TIE2 destabilize microvasculature during pathologic disorders like inflammation cancer. However, scattered reports have also portrayed tumor cells as a source ANGPT2. Employing ISH-based detection ANGPT2,...
Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route metastasis. However, due to lack suitable modeling tools, its contribution long-term disease outcome relevance for therapy remain controversial. Here, we established genetically engineered mouse model (GEMM) fragment-based tumor uniquely sustaining functional network intratumoral lymphatics that facilitates seeding fatal peripheral metastases. Multiregimen survival studies...
Background: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented myeloid-derived suppressor cells (MDSC). However, relative contribution polymorphonuclear (PMN) and monocytic (M) MDSC subsets progression is not clear. Here, we compared both regarding their capacity recruitment mechanisms. Furthermore, inhibited PMN-MDSC migration vivo determine its...
Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified proteolytically cleaved fragments angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic antitumorigenic contributors in communication ecosystem. Preclinical studies multiple tumor models revealed that C-terminal fragment (cANGPTL4) promoted growth metastasis. In contrast, N-terminal ANGPTL4 (nANGPTL4)...
Cancer-associated fibroblasts (CAFs) represent a central cell population of the tumor microenvironment (TME). Recently, single-cell RNA-sequencing (scRNA-seq) analyses primary tumors different cancer entities yielded classifications CAF subsets underscoring heterogeneity CAFs within TME. Here, we analyzed transcriptional signatures approximately 8400 and normal by scRNA-seq compared genetic profiles from murine melanoma to corresponding lung metastases. This revealed distinct for...
Report17 April 2020Open Access Source DataTransparent process Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody Mahak Singhal orcid.org/0000-0002-7303-9585 Division Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany European for Angioscience (ECAS), Medical Faculty Mannheim, University, Biosciences, Search more papers by this author Nicolas Gengenbacher Silvia La Porta Stephanie...
Abstract A lack of advanced preclinical mouse tumor models impedes the progress in urothelial carcinoma research. We present here a novel fast, robust, reliable, and highly reproducible model for genetic induction bladder cancer immunocompetent mice. Different sets oncogenic transposons ( Cmyc , Kras ) Cre drivers were transfected into murine wall two different backgrounds Trp53 fl/fl Braf V600E Pten Ctnnb1 exon3-fl/fl ). Transfection was carried out using vivo electroporation after surgical...
Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) were shown to be an active and pivotal cell population, supporting many protumorigenic mechanisms. Podoplanin (PDPN)-positive CAFs are of special interest since their abundance correlated with a worse prognosis for patients different cancer entities, including malignant melanoma. In this study, we applied loss-of-function approach in vivo mouse melanoma model evaluate contribution CAF-specific PDPN expression...
<div>Abstract<p>The angiopoietin (Angpt)–TIE signaling pathway controls vascular maturation and maintains the quiescent phenotype of resting vasculature. The contextual agonistic antagonistic Tie2 ligand ANGPT2 is believed to be exclusively produced by endothelial cells, disrupting constitutive ANGPT1–TIE2 destabilize microvasculature during pathologic disorders like inflammation cancer. However, scattered reports have also portrayed tumor cells as a source ANGPT2. Employing...
<p>This file consists of supplementary figures (SF) 1-11 consisting of: SF1: Melanoma cells express ANGPT2 (A-F). SF2: cell-expressed Angpt2 does not modulate tumor cell proliferation (A-B). SF3: Tumor knockdown impact growth primary tumors (A-J). SF4: Angpt2-depletion in melanoma affect microenvironment SF5: alters pathways governing metastasis and oxidative stress SF6: affects the cellular redox balance (A-G). SF7: mitochondrial dynamics (A-E). SF8: promotes SF9: early stages vitro...
<p>This file consists of supplementary figures (SF) 1-11 consisting of: SF1: Melanoma cells express ANGPT2 (A-F). SF2: cell-expressed Angpt2 does not modulate tumor cell proliferation (A-B). SF3: Tumor knockdown impact growth primary tumors (A-J). SF4: Angpt2-depletion in melanoma affect microenvironment SF5: alters pathways governing metastasis and oxidative stress SF6: affects the cellular redox balance (A-G). SF7: mitochondrial dynamics (A-E). SF8: promotes SF9: early stages vitro...
<p>Supplementary Figures S1 - S28</p>
<div>Abstract<p>Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route metastasis. However, due to lack suitable modeling tools, its contribution long-term disease outcome relevance for therapy remain controversial. Here, we established genetically engineered mouse model (GEMM) fragment–based tumor uniquely sustaining functional network intratumoral lymphatics that facilitates seeding fatal peripheral metastases....
<p>Supplementary Figures S1 - S28</p>
<div>Abstract<p>The angiopoietin (Angpt)–TIE signaling pathway controls vascular maturation and maintains the quiescent phenotype of resting vasculature. The contextual agonistic antagonistic Tie2 ligand ANGPT2 is believed to be exclusively produced by endothelial cells, disrupting constitutive ANGPT1–TIE2 destabilize microvasculature during pathologic disorders like inflammation cancer. However, scattered reports have also portrayed tumor cells as a source ANGPT2. Employing...
<div>Abstract<p>Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route metastasis. However, due to lack suitable modeling tools, its contribution long-term disease outcome relevance for therapy remain controversial. Here, we established genetically engineered mouse model (GEMM) fragment–based tumor uniquely sustaining functional network intratumoral lymphatics that facilitates seeding fatal peripheral metastases....