A5103220341- Angiogenesis and VEGF in Cancer
- Zebrafish Biomedical Research Applications
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Cardiovascular Disease and Adiposity
- Adipokines, Inflammation, and Metabolic Diseases
- Hippo pathway signaling and YAP/TAZ
- Evolution and Genetic Dynamics
- Cancer Cells and Metastasis
- Evolutionary Game Theory and Cooperation
- Lymphatic System and Diseases
- Prostate Cancer Treatment and Research
- Biomarkers in Disease Mechanisms
- Fibroblast Growth Factor Research
- Urologic and reproductive health conditions
- Erythropoietin and Anemia Treatment
- Diet and metabolism studies
- Systemic Lupus Erythematosus Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Corneal Surgery and Treatments
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Thermoregulation and physiological responses
- Nuclear Structure and Function
- Peripheral Artery Disease Management
Karolinska Institutet
2010-2022
Gangneung Asan Hospital
2022
University of Ulsan
2022
Ulsan College
2022
Center for Rheumatology
2018
Duke-NUS Medical School
2016
Svenska Örtmedicinska Institute
2013
Emory University
2005-2008
The University of Melbourne
2007
Fred Hutch Cancer Center
2005
Significance We show that vascular pericytes significantly contribute to cancer invasion and metastasis by the mechanism of pericyte–fibroblast transition (PFT). This study proposes this concept indicates pericyte’s role. Vascular were considered remodel tumor vessels toward a mature phenotype. However, once dissociated from their functions within tissue are not known. In present study, we pericytes, detached microvasculatures, underwent differentiation become stromal fibroblasts, which...
Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E−/− [ApoE−/−] and LDL receptor−/− [Ldlr−/−] mice), persistent cold exposure stimulated plaque growth by increasing lipid...
Glucose uptake is essential for cancer glycolysis and involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use to harness energy their infinite growth, invasion metastasis2,7,8. Activation thermogenic metabolism brown tissue (BAT) by cold drugs instigates blood glucose adipocytes4,5,9. However, the functional effects global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure tumour-bearing mice conditions markedly...
Abstract Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes reactive oxygen species serving as mediators. The evolved are highly inductive of PCa growth mice, expressed increased levels extracellular matrix (versican tenascin) chemokine (BDFN, CCL5, CXCL5, CXCL16) genes. These genes were validated clinical tissue and/or serum specimens could be the predictors for invasive...
Significance Cancer metastasis is responsible for a majority of the mortality in cancer patients and involves complex interactions, modulated by various factors cytokines, between malignant host cells. Vascular structures solid tumors are crucial cell intravasation into circulation. Our present work shows that VEGF-B produced tumor cells significantly remodels microvasculature, leading to leaky vascular networks highly permissive invasion. VEGF-B–promoted occurs through VEGF-A–independent...
Abstract The impact of discontinuation anti-VEGF cancer therapy in promoting metastasis is unknown. Here we show treatment creates a time-window profound structural changes liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes the fenestrated endothelium loss VE-cadherin. drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation extravasation. Discontinuation an antibody-based sunitinib markedly promotes metastasis....
Abstract Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis UCP1-dependent thermogenesis in mouse brown white adipose tissues. Here we show that endothelial production of PDGF-CC during tissue (WAT) regulates WAT browning. We find genetic deletion VEGFR2, knockout the Pdgf-c gene or pharmacological blockade PDGFR-α impair WAT-beige transition. further stimulation upregulates UCP1 expression acquisition a beige phenotype differentiated WAT-PDGFR-α +...
Angiogenesis plays an instrumental role in the modulation of adipose tissue mass and metabolism. Targeting vasculature provides outstanding opportunity for treatment obesity metabolic disorders. Here, we report physiological functions VEGFR1 angiogenesis, obesity, global Pharmacological inhibition genetic deletion endothelial augmented angiogenesis browning subcutaneous white tissue, leading to elevated thermogenesis. In a diet-induced model, endothelial-VEGFR1 deficiency demonstrated potent...
Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary is microscopic size. In particular, interaction malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting remains largely unknown. Here, we investigated role CAFs facilitating initial events cancer tumors were sizes.Experimental Design: Multicolor-coded and coimplanted into transparent zebrafish body single-cell level was monitored living animals. Healthy...
Placental growth factor (PlGF) remodels tumor vasculatures toward a normalized phenotype, which affects growth, invasion and drug responses. However, the coordinative spatiotemporal relation between PlGF VEGF in modulation of angiogenesis vascular remodeling is less understood. Here we report that positively negatively modulate angiogenesis, through VEGF-dependent mechanism. In two independent models, show inhibited displayed marked effect, leading to microvessels with infrequent branches...
Abstract Understanding the molecular mechanisms regulating beige adipocyte formation may lead to development of new therapies combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation preadipocytes into adipocytes. We identify miR-327 as one most downregulated miRNAs targeting growth factors in stromal-vascular fraction (SVF) under conditions promote white adipose tissue (WAT) browning mice. Gain- and loss-of-function experiments reveal targets...
Significance The etiology and mechanisms underlying the age-related high incidence of metabolic diseases such as type 2 diabetes are not fully understood. In this paper, we show that blood vasculatures in adipose tissues experience continuous changes during aging VEGF is a key angiogenic factor controlling microvessel numbers functions. Surprisingly, targeting receptor by specific blocking drugs produces different sometimes opposing effects on white adipocytes, resulting marked differences...
Chemotherapy-induced broad toxicities are the leading cause of drug-induced mortality in cancer patients. Antiangiogenic drugs (ADs) combination with chemotherapy widely used as front-line therapy for treatment various human cancers. However, beneficial mechanisms underlying poorly understood. Here we show that, several murine tumor models, administration sunitinib markedly reduced chemotherapy-induced bone marrow toxicity. Intriguingly, a sequential regimen, delivery ADs followed by...
Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that VEGF markedly induced sinusoidal vasculature dilation in (BM) BMC to tumors peripheral tissues mouse human models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked mobilization. Genetic deletion of Vegfr2 endothelial cells ablated VEGF-stimulated Conversely, the tyrosine kinase domain from Vegfr1 gene (Vegfr1(TK-/-)) did...
Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that microvascular density tissues where tumors originate a crucial determinant for neovascularization. In three independent including breast cancer, melanoma, fibrosarcoma, inoculation cells subcutaneous tissue, white tissue (WAT), brown (BAT) resulted markedly differential rates angiogenesis,...
Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that associated to development of metabolic disorders, cardiovascular disease, cancer. Here, we present a new concept turn visceral into beneficial energy consumption depot, which for improvement dysfunctions in obese mice. We show low temperature-dependent browning caused decreased weight, total body mass index, despite increased food intake. In high-fat diet-fed mice, temperature exposure improved fat, global...