A5059413396- Angiogenesis and VEGF in Cancer
- Cancer Cells and Metastasis
- Axon Guidance and Neuronal Signaling
- Lymphatic System and Diseases
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer, Lipids, and Metabolism
- Inflammatory mediators and NSAID effects
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- 3D Printing in Biomedical Research
- Neonatal Respiratory Health Research
- Apelin-related biomedical research
- Immune cells in cancer
- MicroRNA in disease regulation
- Kruppel-like factors research
- Phagocytosis and Immune Regulation
- Wnt/β-catenin signaling in development and cancer
- Mechanisms of cancer metastasis
- Fatty Acid Research and Health
- Cancer Research and Treatments
- Congenital Diaphragmatic Hernia Studies
- Protease and Inhibitor Mechanisms
- Sympathectomy and Hyperhidrosis Treatments
Boston Children's Hospital
2016-2025
Harvard University
2016-2025
Boston Children's Museum
2014-2024
Rockefeller University
2024
Dana-Farber/Harvard Cancer Center
2020
Center for Vascular Biology Research
2004-2019
National Institutes of Health
2015
Haukeland University Hospital
2013
University of Bergen
2013
Cornell University
2013
Here, we report that lipocalin 2 (Lcn2) promotes breast cancer progression, and identify the mechanisms underlying this function. We first found Lcn2 levels were consistently associated with invasive in human tissue urine samples. To investigate function of was overexpressed cells to up-regulate mesenchymal markers, including vimentin fibronectin, down-regulate epithelial marker E-cadherin, significantly increase cell motility invasiveness. These changes expression are hallmarks an...
Targeted delivery of therapeutics to tumor neovasculature is potentially a powerful approach for selective cancer treatment. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and signaling, their expression commonly upregulated cancers inflammatory diseases. The αvβ3 integrin differentially on angiogenic endothelial cells as well many cells. Here we demonstrate the differential targeting cisplatin prodrug-encapsulated poly(d,l-lactic-co-glycolic...
Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs raise EET levels in clinical trials for the treatment of hypertension many other diseases. However, despite their pleiotropic effects on cells, little is known about role these epoxyeicosanoids cancer. Here, using genetic pharmacological manipulation endogenous levels, we...
Cancer therapy reduces tumor burden by killing cells, yet it simultaneously creates cell debris that may stimulate inflammation and growth. Thus, conventional cancer is inherently a double-edged sword. In this study, we show cells killed chemotherapy or targeted (“tumor debris”) primary growth when coinjected with subthreshold (nontumorigenic) inoculum of triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited...
Neuropilin-1 (NRP1) is a 130-kDa transmembrane receptor for semaphorins, mediators of neuronal guidance, and vascular endothelial growth factor 165 (VEGF ), an angiogenesis factor. A 2.2-kb truncated NRP1 cDNA was cloned that encodes 644-aa soluble (sNRP1) isoform containing just the a/CUB b/coagulation homology extracellular domains NRP1. sNRP1 secreted by cells as 90-kDa protein binds VEGF , but not 121 . It inhibits 125 I-VEGF binding to tumor -induced tyrosine phosphorylation KDR in...
Melanoma is the most lethal skin cancer. Most deaths from melanoma result metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but effects of semaphorins on tumor metastasis not documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human lines vitro vivo, which suggested it may be a inhibitor. Metastatic cells were transfected with SEMA3F implanted into mice; resultant tumors did metastasize. Rather, primary...
Abstract Epidermal growth factor (EGF) receptor family members are expressed by tumor cells and contribute to progression. The expression activity of EGF receptors in endothelial less well characterized. Analysis tumor-derived showed that they express EGFR, ErbB2, ErbB4, whereas their normal counterparts ErbB3, ErbB4. gain EGFR the loss ErbB3 vasculature was also observed vivo. As a consequence expressing responded other activating both downstream mitogen-activated protein kinase pathway,...
Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ tissue regeneration remains unknown. EETs are predominantly endothelium. Normal require an active paracrine microvascular endothelium, which turn depends angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate via production bioactive...
Significance Strong epidemiologic evidence indicates that aspirin is a powerful antitumorigenic agent. We now demonstrate aspirin-triggered resolvins achieve the antitumor and chemopreventive activity of without toxicity, identifying mechanism for aspirin’s anticancer activity. Our results suggest differentiating between suppression resolution inflammation highly relevant in cancer biology, revealing class endogenous mechanisms. These have pivotal implications therapy chemoprevention; unlike...
Abstract Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow–derived cells. Here, we show that metastasis-incompetent are also capable generating such microenvironments. However, in these situations, the otherwise prometastatic Gr1+ myeloid cells create a metastasis-refractory microenvironment induction thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. Bone marrow–specific genetic deletion Tsp-1 abolished inhibition...
Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape tumor recurrence. We hypothesized these events could be altered by early blockade of the inflammatory cascade and/or accelerating resolution inflammation. Preoperative, but not postoperative, administration nonsteroidal antiinflammatory drug ketorolac resolvins, family specialized proresolving autacoid mediators, eliminated...
Significance Our study demonstrates that ovarian tumor cell debris generated by front-line chemotherapy promotes growth stimulating the release of proinflammatory cytokines and lipid mediators in microenvironment. Targeting debris-mediated surge protumorigenic factors provides a strategy for enhancing efficacy cytotoxic therapies. Here, we show dual cyclooxygenase-2 (COX-2) soluble epoxide hydrolase (sEH) inhibitor PTUPB prevented chemotherapy-induced cytokine/lipid suppressed...
Cutaneous infantile hemangioma progresses through proliferation and involution phases. Since treatment with interferon, a negative regulator of angiogenesis, accelerates the phase, we hypothesized that cutaneous is associated an imbalance between endogenous positive regulators angiogenesis. We examined 30 specimens [proliferative phase (n=15), involuting (n=8), involuted (n=7)] control human skin (n=17), fixed in formalin embedded paraffin. Routine histology, immunohistochemistry, mRNA situ...
Abstract Therapies for most malignancies are generally ineffective once metastasis occurs. While tumour cells migrate through tissues using diverse strategies, the signalling networks controlling such behaviours in human tumours poorly understood. Here we define a role Diaphanous‐related formin‐3 (DIAPH3) as non‐canonical regulator of that restrains conversion to amoeboid cell behaviour multiple cancer types. The DIAPH3 locus is close RB1 , within narrow consensus region deletion on...