A5030159349- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Lipid Membrane Structure and Behavior
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- CAR-T cell therapy research
- HIV Research and Treatment
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- Cytokine Signaling Pathways and Interactions
- Growth Hormone and Insulin-like Growth Factors
- Glycosylation and Glycoproteins Research
- Protease and Inhibitor Mechanisms
- interferon and immune responses
- Synthesis and biological activity
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- RNA modifications and cancer
- Angiogenesis and VEGF in Cancer
- Cancer Cells and Metastasis
Centro Nacional de Biotecnología
2016-2025
Universidad Autónoma de Madrid
2001-2025
Consejo Superior de Investigaciones Científicas
2006-2024
Centro de Investigación del Cáncer
2017
Hospital Universitario de Fuenlabrada
2017
Hospital Clínico San Carlos
2017
Research Institute Hospital 12 de Octubre
2017
Hospital Universitario Ramón y Cajal
2017
Hospital Universitario de La Princesa
2017
Hospital Universitario La Paz
2013
Redistribution of specialized molecules in migrating cells develops asymmetry between two opposite cell poles, the leading edge and uropod. We show that acquisition a motile phenotype T lymphocytes results asymmetric redistribution ganglioside GM3- GM1-enriched raft domains to uropod, respectively. This segregation each pole parallels specific membrane proteins associated subfraction. Our data suggest partitioning is major determinant for protein polarized cells, as ectopic expression...
Lymphocyte traffic is required to maintain homeostasis and perform appropriate immunological reactions. To migrate into inflamed tissues, lymphocytes must acquire spatial functional asymmetries. Mitochondria are highly dynamic organelles that distribute in the cytoplasm meet specific cellular needs, but whether this essential lymphocyte functions unknown. We show mitochondria specifically concentrate at uropod during migration by a process involving rearrangements of their shape....
Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft–associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. GTPase activity can negatively regulated by statins, family drugs used treat hypercholesterolemia in man. Statins mediate inhibition GTPases impeding prenylation small G proteins through blockade 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show statins decreased viral load and...
The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the to vitronectin collagen in a dose- time-dependent manner, suggesting IGF-I triggers activation different integrins. On other hand, promotes association insulin receptor 1 with focal kinase (FAK), paxillin, tyrosine phosphatase SHP-2, resulting FAK paxillin dephosphorylation. Abrogation SHP-2 catalytic activity...
Chemokines and their receptors direct leukocyte migration among blood, lymph tissues. Evidence has recently accumulated that, besides chemotactic functions, chemokine are highly versatile players that fine tune immune responses. During human T cell activation by antigen-presenting cells, the CCR5 CXCR4 recruited into immunological synapse, where they deliver costimulatory signals. However, molecular mechanisms allowing signaling versatility of unknown. Here, we describe functional...
Spatially restricted activation of signaling molecules governs critical aspects cell migration; the mechanism by which this is achieved nonetheless remains unknown. Using time-lapse confocal microscopy, we analyzed dynamic redistribution lipid rafts in chemoattractant-stimulated leukocytes expressing glycosyl phosphatidylinositol–anchored green fluorescent protein (GFP-GPI). Chemoattractants induced persistent GFP-GPI to leading edge raft (L raft) and uropod Jurkat, HL60, dimethyl...
To elucidate the physiological role of human stromelysin-3 (hST-3) in tumor progression and/or wound healing, insulin-like growth factor-binding protein-1 (IGFBP-1) was analyzed as a potential substrate. hST-3 proteolysis generates two fragments 16 and 9 kDa that react with IGFBP-1 monoclonal antibody, although they do not bind factor-I (IGF-I) ligand blot. N-terminal sequencing shows cleaves at His140-Val141 bond located midregion. We show inhibits IGF-I-induced survival proliferation BAF/3...
ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond these treatments most them eventually relapse. The existence this population particularly non-responding or relapsing urges the search for novel purpose study was determine whether cannabinoids might constitute new therapeutic tool treatment tumors. We analyzed...
Abstract Introduction Dysregulated NOTCH receptor activity has been implicated in breast cancer but the mechanisms by which contributes to transformation are not yet clear, as it context-dependent effects on properties of transformed cells. Methods We have used various vitro and vivo carcinogenic models analyze impact Notch signaling onset progression tumors. Results found that ectopic expression Notch1 intracellular domain (N1ICD) MCF-7 adenocarcinoma cell line caused reduction...
Abstract Immune responses against cancer rely upon leukocyte trafficking patterns that are coordinated by chemokines. CCR5, the receptor for chemotactic chemokines MIP1alpha, MIP1beta, and RANTES (CCL3, CCL4, CCL5), exerts major regulatory effects on CD4+- CD8+ T cell-mediated immunity. Although CCR5 its ligands participate in response to various pathogens, relevance tumoral immune control has been debated. Here, we report a specific, ligand-dependent role optimizing antitumor responses. In...
<h3>Background</h3> Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion activated T cells. Blockade PD-1 pathway is widely used for cancer treatment, yet transduced by in cells remain elusive. <h3>Methods</h3> Expression profiles human CD8<sup>+</sup> resting, (CD3 + CD28) and PD-1-stimulated CD28 PD-L1-Fc) conditions were evaluated RNA-seq. Bioinformatic analyses identify signaling pathways differentially regulated...
M1 and M2 macrophage phenotypes, which mediate proinflammatory antiinflammatory functions, respectively, represent the extremes of immunoregulatory plasticity in population. This can also result intermediate states that support a balance between these opposing functions. In sepsis, macrophages compensate for hyperinflammation by acquiring an M2-like immunosuppressed status increases risk secondary infection death. The to reprogramming develops during LPS tolerance resembles pathological...
The androgen-independent human prostate adenocarcinoma cell line DU-145 proliferates in serum-free medium and produces insulin-like growth factors (IGF)-I, IGF-II, the IGF type-1 receptor (IGF-1R). They also secrete three IGF-binding proteins (IGFBP), IGFBP-2, -3, -4. Of these, immunoblot analysis revealed selective proteolysis of IGFBP-3, yielding fragments 31 19 kDa. By using an anti-IGF-I-specific monoclonal antibody (mAb), we detect surface receptor-bound IGF-I on serum-starved cells,...
Association of matrix metalloprotease 9 (MMP9) to the cell membrane is considered important in tumor growth and angiogenesis. To dissect this regulatory mechanism, we generated raft non-raft MMP9 chimeras force expression MCF-7 human breast carcinoma line. targeting surface domains rendered a constitutive active form, suggesting contribution by lipid environment MMP activation. We cancer xenograft models using cells overexpressing secreted membrane-anchored MMP9. The chimera was...
Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity breast cells through pertussis toxin-, JAK2-, and p38 mitogen-activated protein kinase-dependent mechanisms. blockade significantly enhanced proliferation xenografts from bearing wild-type p53, but did not a mutation. In parallel, data obtained primary...