A5046908569- Angiogenesis and VEGF in Cancer
- Axon Guidance and Neuronal Signaling
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Caveolin-1 and cellular processes
- Cellular Mechanics and Interactions
- Liver physiology and pathology
- Zebrafish Biomedical Research Applications
- Cellular transport and secretion
- Lymphatic System and Diseases
- Cancer-related gene regulation
- Cancer Mechanisms and Therapy
- Mathematical Biology Tumor Growth
- Microtubule and mitosis dynamics
- Lipid metabolism and disorders
- Biomarkers in Disease Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cancer Treatment and Pharmacology
- Immune cells in cancer
- Ion Channels and Receptors
- Tissue Engineering and Regenerative Medicine
- Protease and Inhibitor Mechanisms
- Apelin-related biomedical research
Candiolo Cancer Institute
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2025
University of Turin
2015-2024
Tufts Medical Center
2021
Fondazione Piemontese per la Ricerca sul Cancro Onlus
2003-2013
Technion – Israel Institute of Technology
2012
Cancer Research UK Scotland Institute
2012
International Centre for Genetic Engineering and Biotechnology
2012
University of Trieste
2012
University of Padua
2006
Transforming growth factor-beta1 (TGFbeta1), a major promoter of myofibroblast differentiation, induces alpha-smooth muscle (sn) actin, modulates the expression adhesive receptors, and enhances synthesis extracellular matrix (ECM) molecules including ED-A fibronectin (FN), an isoform de novo expressed during wound healing fibrotic changes. We report here that FN deposition precedes alpha-SM actin by fibroblasts granulation tissue evolution in vivo after TGFbeta1 stimulation vitro. Moreover,...
Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165 (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1 null embryos display defects that differ from those of mice lacking either or Sema3A proteins. Furthermore, it has been recently reported required cell (EC) response to both VEGF-A165 VEGF-A121 isoforms, the latter being incapable binding on EC surface. Taken together, these data suggest phenotype caused by loss could be due...
Experiments of in vitro formation blood vessels show that cells randomly spread on a gel matrix autonomously organize to form connected vascular network. We propose simple model which reproduces many features the biological system. both and real system exhibit fractal behavior at small scales, due process migration dynamical aggregation, followed large scale by random percolation coalescence aggregates. The results are good agreement with analysis performed experimental data.
Tumor growth and progression rely upon angiogenesis, which is regulated by pro- antiangiogenic factors, including members of the semaphorin family. By analyzing 3 different mouse models multistep carcinogenesis, we show here that during 3A (Sema3A) expressed in ECs, where it serves as an endogenous inhibitor angiogenesis present premalignant lesions lost tumor progression. Pharmacologic inhibition Sema3A angiogenic switch, point when pretumoral initiate phase persists throughout growth,...
Cancer development, progression, and metastasis are highly dependent on angiogenesis. The use of antiangiogenic drugs has been proposed as a novel strategy to interfere with tumor growth, but cancer cells respond by developing strategies escape these treatments. In particular, animal models show that currently used in clinical settings reduce tissue oxygenation trigger molecular events foster resistance therapy. Here, we semaphorin 3A (Sema3A) expression overcomes the proinvasive...
During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries mural cells. In our study, we hypothesized that Ang-1/Tie2 system could cross-talk with integrins, be influenced by dynamic interactions between extracellular matrix endothelial cells (ECs). Here, show α5β1 specifically sensitizes modulates receptor activation signaling, allowing EC survival at low concentrations Ang-1...
MET, the high-affinity receptor for hepatocyte growth factor, is frequently deregulated in human cancer. Tivantinib (ARQ197; Arqule), a staurosporine derivative that binds to dephosphorylated MET kinase vitro, being tested clinically as highly selective inhibitor. However, mechanism of action tivantinib still unclear.The activity was analyzed multiple cellular models, including: cells displaying c-MET gene amplification, strictly 'addicted' signaling; with normal copy number, not dependent...
During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. is mainly expressed in vascular cells, where it induces adhesion to extracellular matrix (ECM) unknown mechanisms. We identify Ras Rab5 interacting protein RIN2 as a key effector endothelial cells interacts with mediates pro-adhesive -angiogenic activity R-Ras. Both R-Ras-GTP localize at nascent ECM sites associated...
Besides the regulation of hematopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) induces expression a functional program in cultured endothelial cells (ECs) related to angiogenesis and their survival bone marrow microenvironment. ECs express specific GM-CSF receptor that signals through recruitment activation Janus kinase (JAK)2 (Soldi et al., Blood 89, 863-872, 1987). We now report vivo activates JAK-2 signal transducers activators transcription (STAT)-3. This cytokine has...
Abstract Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 widely expressed in cancer cells and advanced human tumors; however, its functional relevance signaling mechanisms are unclear. Here, we show that expression controls viability proliferation of different cells, independent short intracellular tail. We found the domain interacts with EGF receptor (EGFR) promotes cascade elicited upon or TGF-α stimulation. Upon silencing, ability ligand-bound EGFR to cluster...
Abstract Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating α5β1 integrin-mediated extracellular FN endocytosis exocytosis newly synthesized remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active is recycled to the EC surface. We identify pathway, comprising regulators post-Golgi carrier formation PI4KB AP-1A, small GTPase Rab11B, surface...
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing motility. However, mechanisms which it could influence vascular behavior unknown. Here, we reveal novel non-channel function for that unexpectedly acts as Rap1 GTPase inhibitor, thereby inhibiting endothelial motility, independently pore...
Article19 February 2020Open Access Source DataTransparent process Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits Eloina Corradi Department Cellular, Computational Integrative Biology - CIBIO, University Trento, Italy Search for more papers by this author Irene Dalla Costa Antoneta Gavoci Archana Iyer Michela Roccuzzo Tegan A Otto Eleonora Oliani Simone Bridi Stephanie Strohbuecker Gabriela Santos-Rodriguez Unidad de Genómica Avanzada...
Integrin activation is a multifaceted phenomenon leading to increased affinity and avidity for matrix ligands. To investigate whether cytokines produced during stromal infiltration of carcinoma cells activate nonfunctional epithelial integrins, cellular system human thyroid clones derived from normal glands (HTU-5) papillary carcinomas (HTU-34) was employed. In HTU-5 cells, αvβ3 integrin diffused all over the membrane, disconnected cytoskeleton, unable mediate adhesion. Conversely, in HTU-34...
BACK: The functional organization of polarized epithelia depends mostly on adhesion molecules belonging to the integrin and cadherin families. These either recognize basement membrane components, such as laminins, or form intercellular junctions via homotypic interactions. Such tissue is often disrupted upon neoplastic transformation, resulting loss polarization cell cohesion might be a prerequisite for invasive metastatic behavior carcinomas.We studied modifications thyroid adhesive...
The ability of cells to sense spatial gradients chemoattractant factors governs the development complex eukaryotic organisms. Cells exposed shallow respond with strong accumulation enzyme phosphatidylinositol 3-kinase (PI3K) and its D3-phosphoinositide product (PIP 3 ) on plasma membrane side highest concentration, whereas PIP -degrading PTEN 2 localize in a complementary pattern. Such an early symmetry-breaking event is mandatory step for directed cell movement elicited by chemoattractants,...
Improving tumor perfusion, thus tempering tumor-associated hypoxia, is known to impair cancer progression. Previous work from our laboratory has shown that VEGF-A165 and semaphorin 3A (Sema3A) promote vessel maturation through the recruitment of a population circulating monocytes expressing neuropilin-1 (Nrp1) receptor (Nrp1-expressing monocytes; NEM). Here, we define characteristics bone marrow NEMs assess whether these cells might represent an exploitable tool induce maturation. Gene...
An NRP1-independent, non-natural SEMA3A mutant isoform is a parenterally deliverable anticancer drug that normalizes the vasculature.