Mónica Sala-Valdés - Academia.edu (original) (raw)

Papers by Mónica Sala-Valdés

Trends in Cell Biology, 2009

Journal of Leukocyte Biology, 2004

B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a res... more B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a result of the differential expression of chemokine receptors. We found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5, the main chemokine receptors that mediate B cell entry into secondary lymphoid tissues and their homing to T cell and B cell zones therein, were highly expressed in B malignancies with widespread involvement of lymph nodes. Conversely, those pathologies with little or no nodular dissemination showed no expression to very low levels of CCR7 and CXCR5 and low to moderate levels of CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in determining the pattern of lymphoid organ involvement of B tumors. Functional studies were performed on B malignancies expressing different levels of CCR7, CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and did not migrate in response to their ligands; a moderate expression of CXCR4 on MM cells was accompanied by a migratory response to its ligand, CXCL12. By contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the highest levels of these chemokine receptors and efficiently migrated in response to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B-CLL cells in response to both of the CCR7 ligands correlated with the presence of clinical lymphadenopathy, thus indicating that the high expression of functional chemokine receptors justifies the widespread character of B-CLL, representing a clinical target for the control of tumor cell dissemination.

Journal of Cell Science, 2012

In this study, we describe that the PDZ protein syntenin-1 is a crucial element for the generatio... more In this study, we describe that the PDZ protein syntenin-1 is a crucial element for the generation of signaling asymmetry during the cellular response to polarized extracellular cues. We analyze the role of syntenin-1 in the control of asymmetry in two independent models of T cell polarization – the migratory response to chemoattractants and the establishment of cognate interactions between T cells and antigen-presenting cells (APCs). A combination of mutant, biochemical and siRNA approaches demonstrate that syntenin-1 is vital for the generation of polarized actin structures such as the leading edge and the contact zone with APCs. We found that the mechanism by which syntenin-1 controls actin polymerization relies on its mandatory role for activation of the small GTPase Rac. Syntenin-1 controls Rac through a specific association with the myosin phosphatase Rho interacting protein (M-RIP), which occurs in response to phosphorylation of syntenin-1 by Src at Tyr4. Our data indicate th...

Journal of Biological Chemistry, 2006

EWI-2 and EWI-F, two members of a novel subfamily of Ig proteins, are direct partners of tetraspa... more EWI-2 and EWI-F, two members of a novel subfamily of Ig proteins, are direct partners of tetraspanins CD9 (Tspan29) and CD81 (Tspan28). These EWI proteins contain a stretch of basic charged amino acids in their cytoplasmic domains that may act as binding sites for actin-linking ezrin-radixin-moesin (ERM) proteins. Confocal microscopy analysis revealed that EWI-2 and EWI-F colocalized with ERM proteins at microspikes and microvilli of adherent cells and at the cellular uropod in polarized migrating leukocytes. Immunoprecipitation studies showed the association of EWI-2 and EWI-F with ERM proteins in vivo. Moreover, pulldown experiments and protein-protein binding assays with glutathione S-transferase fusion proteins containing the cytoplasmic domains of EWI proteins corroborated the strong and direct interaction between ERMs and these proteins. The active role of ERMs was further confirmed by double transfections with the N-terminal domain of moesin, which acts as a dominant negative form of ERMs, and was able to delocalize EWIs from the uropod of polarized leukocytes. In addition, direct association of EWI partner CD81 C-terminal domain with ERMs was also demonstrated. Functionally, silencing of endogenous EWI-2 expression by short interfering RNA in lymphoid CEM cells augmented cell migration, cellular polarity, and increased phosphorylation of ERMs. Hence, EWI proteins, through their direct interaction with ERM proteins, act as linkers to connect tetraspanin-associated microdomains to actin cytoskeleton regulating cell motility and polarity. Recent reports have described a novel Ig subfamily named EWI proteins because of their characteristic Glu-Trp-Ile (EWI) extracellular motif (1-5). This subfamily includes the following four members: EWI-2 (also called PGRL in mouse), EWI-3, EWI-F/CD9P-1, and EWI-101. EWI-2 and EWI-F proteins have short cytoplasmic tails of 10 and 27 amino acids and an * This work was supported in part by Biología Fundamental 2005-08435/Biología Molecular y Celular from the Spanish Ministry of Education and Science and the Ayuda a la Investigació n Básica 2002 from Juan March Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Expert Opinion on Therapeutic Targets, 2012

Tetraspanins are a family of small proteins that cross the membrane four times and form complexes... more Tetraspanins are a family of small proteins that cross the membrane four times and form complexes by interacting between themselves and with a variety of transmembrane and cytosolic proteins, building a network of interactions referred to as tetraspanin web or tetraspanin enriched microdomains (TEMs). These domains provide a signaling platform involved in many important cellular functions and malignant processes. The authors describe the methods and the rationale for targeting tetraspanins in the therapy of cancer in this review. Targeting tetraspanins in cancer may be a promising therapy due to the importance of tetraspanins in several steps of tumor formation, communication with the environment, dissemination, and metastasis.

Cardiovascular Pathology, 2004

Blood, 2008

MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found ... more MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner α3β1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming α3β1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane do...

Blood, 2005

Tetraspanins associate with several transmembrane proteins forming microdomains involved in inter... more Tetraspanins associate with several transmembrane proteins forming microdomains involved in intercellular adhesion and migration. Here, we show that endothelial tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Alteration of endothelial tetraspanin microdomains by CD9–large extracellular loop (LEL)–glutathione S–transferase (GST) peptides or CD9/CD151 siRNA oligonucleotides interfered with ICAM-1 and VCAM-1 function, preventing lymphocyte transendothelial migration and increasing lymphocyte detachment under shear flow. Heterotypic intercellular adhesion mediated by VCAM-1 or ICAM-1 was augmented when expressed exogenously in the appropriate tetraspanin environment. Therefore, tetraspanin microdomains have a crucial role in the proper adhesive function of ICAM-1 and VCAM-1 during leukocyte adhesion and transendothelial migration.

doi:10.1182/blood-2008-02-139394 Prepublished online Jul 28, 2008;2008 112: 3217-3226€€€€Arroyo a... more doi:10.1182/blood-2008-02-139394 Prepublished online Jul 28, 2008;2008 112: 3217-3226€€€€Arroyo and Francisco Sanchez-Madrid Sachs, Monica Sala-Valdes, Miguel A. Alonso, Maria C. Montoya, Arnoud Sonnenberg, Alicia G. Maria Yanez-Mo, Olga Barreiro, Pilar Gonzalo, Alicia Batista, Diego Megias, Laura Genis, Norman€

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primar... more MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells Authors: María Yánez-Mó, Olga Barreiro, Pilar Gonzalo, Alicia Batista, Diego Megías, Laura Genís, Norman Sachs, Mónica Sala-Valdés, Miguel A. Alonso, María C. Montoya, Arnoud Sonnenberg, Alicia G. Arroyo, and Francisco Sánchez-Madrid Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid. Madrid, Spain. Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Consejo Superior de Investigaciones Científicas, Madrid, Spain. Centro Nacional de Investigaciones Oncológicas, Madrid, Spain 5 Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, Netherlands. Running title: Regulation of MT1-MMP activity by tetraspanin CD151 Scientific Category: Hemostasis, Trombosis and Vascular Biology Abreviations: HUVEC: Human umbilical vein endothelial cells MLE...

Maria Yanez-MoKolesnikova, Jesus Vazquez, Francisco Sanchez-Madrid andLopez-Martin, Angeles Ursa,... more Maria Yanez-MoKolesnikova, Jesus Vazquez, Francisco Sanchez-Madrid andLopez-Martin, Angeles Ursa, Susana Alvarez, Tatiana V.Rocha-Perugini, Daniel Perez-Hernandez, Soraya Monica Gordon-Alonso, Monica Sala-Valdes, Verahttp://www.jimmunol.org/content/189/2/689doi: 10.4049/jimmunol.11037082012;J Immunol€2012; 189:689-700; Prepublished online 11 JuneMaterialSupplementary8.DC1.htmlhttp://www.jimmunol.org/content/suppl/2012/06/11/jimmunol.110370Referenceshttp://www.jimmunol.org/content/189/2/689.full#ref-list-1This article cites 70 articles, 38 of which you can access for free at: Subscriptionshttp://jimmunol.org/subscriptionsInformation about subscribing to The Journal of Immunology is online at: Permissionshttp://www.aai.org/ji/copyright.htmlSubmit copyright permission requests at: Email Alertshttp://jimmunol.org/cgi/alerts/etocReceive free email-alerts when new articles cite this article. Sign up at:

Las tetraspaninas se caracterizan por su capacidad de interaccionar unas con otras y con otras pr... more Las tetraspaninas se caracterizan por su capacidad de interaccionar unas con otras y con otras proteinas organizando en la membrana plasmatica microdominios denominados ?Microdominios ricos en Tetraspaninas? o ?Red de Tetraspaninas?. EWI-2 y EWI-F son dos de estas proteinas que pertenecen a la superfamilia de las inmunoglobulinas y que se asocian directamente a las tetraspaninas CD9 y CD81. Este estudio revela la existencia de distintas asociaciones entre las proteinas EWI y CD81 con moleculas adaptadoras del citoesqueleto de actina, conectando los microdominios de tetraspaninas con el entramado de actina y sus moleculas senalizadoras asociadas. En primer lugar, hemos descrito la asociacion directa de los dominios C-terminal de EWI-2, EWI-F y CD81 con el dominio N-terminal de las proteinas ERM Ezrina y Moesina y se ha demostrado el papel regulador negativo de EWI-2 en la migracion y polarizacion de linfocitos T en los que la fosforilacion de ERMs tiene un papel relevante. Respecto a...

British journal of cancer, Jan 30, 2017

In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genet... more In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently muta...

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Bio... more Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 16-07-2010

Frontiers in Physiology, 2014

New therapeutic agents are needed in digestive tract tumors. Co-029/tspan8 is a tetraspanin frequ... more New therapeutic agents are needed in digestive tract tumors. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumors, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don't express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co-029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumor cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic applications.

Tetraspanins, 2013

ABSTRACT Tetraspanin-enriched microdomains (TEMs) are specialized platforms in the plasma membran... more ABSTRACT Tetraspanin-enriched microdomains (TEMs) are specialized platforms in the plasma membrane that include certain adhesion receptors, mainly integrins and receptors of the Ig superfamily. Insertion into TEMs increases the local concentration of these adhesion receptors, facilitating their function as avidity regulators. TEMs also regulate interaction and crosstalk between different receptors at the plasma membrane, as well as their internalization rate. Moreover, certain signaling pathways are regulated by association with tetraspanins. Thus, tetraspanins emerge as critical regulators of biological phenomena involving adhesion to the extracellular matrix or homotypic or heterotypic intercellular interactions. These proteins are implicated in different steps of cancer progression, the regulation of intercellular adhesion between polarized epithelial cells, angiogenesis, antigen presentation and extravasation of leukocytes or tumor cells. In addition, several pathogens hijack these tetraspanin-adhesion platforms to increase their infectivity.

The Journal of Immunology, 2012