A5079213910- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Gastric Cancer Management and Outcomes
- Proteoglycans and glycosaminoglycans research
- Esophageal Cancer Research and Treatment
- Nanoparticle-Based Drug Delivery
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Connective tissue disorders research
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Fibroblast Growth Factor Research
- Metal complexes synthesis and properties
- Immune cells in cancer
- Colorectal Cancer Surgical Treatments
- Hippo pathway signaling and YAP/TAZ
- Electron Spin Resonance Studies
- Glycosylation and Glycoproteins Research
- Ovarian cancer diagnosis and treatment
- Ferroptosis and cancer prognosis
- Bioactive Compounds and Antitumor Agents
- Immunotherapy and Immune Responses
- Organometallic Compounds Synthesis and Characterization
Centro di Riferimento Oncologico
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2025
Thomas Jefferson University
2000-2003
Sidney Kimmel Cancer Center
2000
About 50% of cutaneous melanoma (CM) harbors the activating BRAFV600 mutation which exerts most oncogenic effects through MAPK signaling pathway. In last years, a number modulators have been identified, including Spry1. this context, we recently demonstrated that knockout Spry1 (Spry1KO) in BRAFV600-mutant CM led to cell cycle arrest and apoptosis, repressed proliferation vitro, reduced tumor growth vivo. Despite these findings, however, precise molecular mechanism linking remains be...
Perlecan, a ubiquitous basement membrane heparan sulfate proteoglycan, plays key roles in blood vessel growth and structural integrity. We discovered that the C terminus of perlecan potently inhibited four aspects angiogenesis: endothelial cell migration, collagen-induced tube morphogenesis, chorioallantoic Matrigel plug assays. The was active at nanomolar concentrations blocked adhesion to fibronectin type I collagen, without directly binding either protein; henceforth we have named it...
EMILINs and Multimerins (EMILIN1, EMILIN2, Multimerin1, Multimerin2) constitute a four member family that in addition to the shared C-terminus gC1q domain typical of gC1q/TNF superfamily members contain N-terminus unique cysteine-rich EMI domain. These glycoproteins are homotrimeric assemble into high molecular weight multimers. They predominantly expressed extracellular matrix contribute several cellular functions part associated with not yet assigned nor linked other specific regions...
The goal of this study was to discover novel partners for perlecan, a major heparan sulfate proteoglycan basement membranes, and examine new interactions through which perlecan may influence cell behavior. We employed the yeast two-hybrid system used domain V as bait screen human keratinocyte cDNA library. Among strongest interacting clones, we isolated ∼1.6-kb insert that encoded extracellular matrix protein 1 (ECM1), secreted glycoprotein involved in bone formation angiogenesis. sequencing...
Perlecan is a multifaceted heparan sulfate proteoglycan that expressed not only as an intrinsic constituent of basement membranes but also cell-surface and pericellular proteoglycan. functions ligand reservoir for various growth factors become stabilized against misfolding or proteolysis acts co-receptor basic fibroblast factor by augmenting high affinity binding receptor activation. These biological properties are mediated the moiety. Rather little known about protein core's mediation...
Among the nonplatinum antitumor drugs, gold(III)-dithiocarbamato derivatives have recently attracted considerable attention due to their strong in vitro and vivo antiproliferative activity reduced renal toxicity. Some of them, namely [AuCl(2) (DMDT)] (compound 1) [AuBr(2) (ESDT)] 2), shown be highly active against androgen-resistant prostate cancer cell lines PC3 DU145, both inhibiting proliferation a dose-dependent way, are more than reference drug cisplatin (cis-[PtCl(2) (NH(3) )(2) ]). In...
Classic Hodgkin lymphoma tumor cells express a functional CCR5 receptor, and tissues high CCL5 levels, suggesting that CCL5-CCR5 signaling is involved in tumor-microenvironment formation growth. Using the antagonist, maraviroc, neutralizing anti-CCL5 antibody, we found secreted by classic recruited mesenchymal stromal monocytes. The “education” of cell-conditioned medium enhanced cells’ proliferation secretion. In turn, educated increased clonogenic growth monocyte migration, but these...
Perlecan, a widespread heparan sulfate proteoglycan, functions as bioactive reservoir for growth factors by stabilizing them against misfolding or proteolysis. These factors, chiefly members of the fibroblast factor (FGF) gene family, are coupled to N-terminal chains, which augment high affinity binding and receptor activation. However, rather little is known about biological partners protein core. The major goal this study was identify novel proteins that interact with core perlecan. Using...
In an in vivo search of novel partners for perlecan, a major heparan sulfate proteoglycan basement membranes and cell surfaces, we identified progranulin, secreted growth factor, as strong interacting protein. Unambiguous interaction, first observed with the yeast two-hybrid system, was corroborated by co-immunoprecipitation studies using cell-free transcription/translation transient transfection assays. The interaction progranulin perlecan domain V involved two laminin- epidermal...
AbstractElastin microfibril interface-located proteins (EMILINs) constitute a family of extracellular matrix (ECM) glycoproteins characterized by the presence an EMI domain at N terminus and gC1q C terminus. EMILIN1, archetype molecule family, is involved in elastogenesis hypertension etiology, whereas function EMILIN2 has not been resolved. Here, we provide evidence that expression triggers apoptosis different cell lines. Cell death depends on activation extrinsic apoptotic pathway...
Colorectal cancer is one of the most frequent and deadly tumors. Among key regulators CRC growth progression, microenvironment has emerged as a crucial player possible route for development new therapeutic opportunities. More specifically, extracellular matrix acts directly on cells indirectly affecting behavior stromal inflammatory cells, well bioavailability factors. ECM molecules, EMILIN-2 frequently down-regulated by methylation in purpose this study was to verify impact loss its value...
Anti-angiogenic therapy is an established method for the treatment of several cancers and vascular-related diseases. Most agents employed target vascular endothelial growth factor A, major cytokine stimulating angiogenesis. However, efficacy these treatments limited by onset drug resistance. Therefore, it fundamental importance to better understand mechanisms that regulate angiogenesis microenvironmental cues play significant role influence patient outcome. In this context, here we review...
EMILIN (elastin microfibril interface located protein) is an extracellular matrix glycoprotein abundantly expressed in elastin-rich tissues such as blood vessels, skin, heart, and lung. It occurs associated with elastic fibers at the between amorphous elastin microfibrils. Avian was extracted from 19-day-old embryonic chick aortas vessels purified by ion-exchange chromatography gel filtration. Tryptic peptides were generated sequenced, degenerate inosine-containing oligonucleotide primers...
We have recently reported that elastin microfibril interface located protein 2 (EMILIN2), an extracellular matrix (ECM) glycoprotein, triggers cell death through a direct binding to receptors. EMILIN2 thus influences viability mechanism is unique for ECM molecule. In the present work, we report additional function this First, identify region responsible proapoptotic effects, 90-amino acid residue-long coiled-coil fragment toward N-terminus of The recapitulates mechanisms. addition, using...
Abstract EMILIN2 is an extracellular matrix ( ECM ) protein that exerts contradictory effects within the tumour microenvironment: it induces apoptosis in a number of cells, but also enhances neo‐angiogenesis. In this study, we describe new mechanism by which attenuates cell viability. Based on sequence homology with cysteine‐rich domain CRD Frizzled receptors, hypothesized could affect Wnt signalling activation and demonstrate direct interaction Wnt1 ligand. This physical binding leads to...
Endorepellin, a processed fragment of perlecan protein core, possesses anti-angiogenic activity by antagonizing endothelial cells. Endorepellin contains three laminin G-like (LG) domains and binds simultaneously to vascular growth factor receptor 2 (VEGFR2) α2β1 integrin, resulting in dual antagonism. Treatment cells with endorepellin inhibits transcription VEGFA, the natural ligand for VEGFR2, attenuating pro-survival migratory activities VEGFA/VEGFR2 signaling cascade. Here, we...