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‣ Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations

Fraga, J. S.; Silva, N. A.; Lourenço, A. S.; Gonçalves, V.; Neves, N. M.; Reis, R. L.; Rodrigues, A. J.; Manadas, B.; Sousa, N.; Salgado, A. J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Português
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It has been previously shown that the secretome of Human Umbilical Cord Perivascular Cells (HUCPVCs), known for their mesenchymal like stem cell character, is able to increase the metabolic viability and hippocampal neuronal cell densities. However, due to the different micro-environments of the distinct brain regions it is important to study if neurons isolated from different areas have similar, or opposite, reactions when in the presence of HUCPVCs secretome (in the form of conditioned media-CM). In this work we: 1) studied how cortical and cerebellar neuronal primary cultures behaved when incubated with HUCPVCs CM and 2) characterized the differences between CM collected at two different conditioning time points. Primary cultures of cerebellar and cortical neurons were incubated with HUCPVCs CM (obtained 24 and 96 h after three days of culturing). HUCPVCs CM had a higher impact on the metabolic viability and proliferation of cortical cultures, than the cerebellar ones. Regarding neuronal cell densities it was observed that with 24 h CM condition there were higher number MAP-2 positive cells, a marker for fully differentiated neurons; this was, once again, more evident in cortical cultures. In an attempt to characterize the differences between the two conditioning time points a proteomics approach was followed...

‣ Neospora caninum: estudo do secretoma e caracterização molecular de três proteínas com domínios Apple; Neospora caninum: study of the secretome and molecular characterization of three proteins containing Apple domains

Oliveira, Letícia Pollo de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 08/11/2013 Português
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Neospora caninum (filo Apicomplexa) é um parasita obrigatório intracelular como todos os membros deste filo, alguns reconhecidos por causarem doenças com impacto relevante na saúde humana (Plasmodium e Toxoplasma) e veterinária (Babesia, Eimeria e Cryptosporidium). Causador da neosporose, N. caninum vem emergindo como um dos maiores causadores de abortos infecciosos em bovinos, levando a consideráveis perdas econômicas na bovinocultura mundial. Devido à sua recente descoberta, o conhecimento sobre diversos processos bioquímicos de N.caninum ainda é limitado, demandando novas pesquisas para a compreensão de seus mecanismos de sobrevivência e consequente identificação de alvos para intervenção terapêutica. O processo de invasão celular é bastante investigado em pesquisas envolvendo apicomplexas, uma vez que a sobrevivência desses parasitas depende do sucesso de sua entrada na célula hospedeira. Proteínas secretadas de organelas filo-específicas (micronemas, roptrias e grânulos densos) estão intimamente envolvidas com a invasão celular. Elas são responsáveis pela interação inicial com a célula hospedeira, participam da junção de movimento formada no momento da invasão, e contribuem para a estabilização do vacúolo parasitóforo. Neste trabalho as proteínas secretadas por taquizoítas de N. caninum foram investigadas de duas formas: (1) por caracterização molecular de proteínas com domínio Apple; e (2) por estudo do secretoma do parasita. Os domínios proteicos do tipo Apple são caracterizados pela capacidade de interação proteína-proteína e proteína-carboidrato...

‣ Unravelling the Neospora caninum secretome through the secreted fraction (ESA) and quantification of the discharged tachyzoite using high-resolution mass spectrometry-based proteomics

Pollo-Oliveira, Leticia; Post, Harm; Acencio, Marcio Luis; Lemke, Ney; van den Toorn, Henk; Tragante, Vinicius; Heck, Albert J. R.; Altelaar, A. F. Maarten; Yatsuda, Ana Patricia
Fonte: Biomed Central Ltd. Publicador: Biomed Central Ltd.
Tipo: Artigo de Revista Científica Formato: 14
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Processo FAPESP: 05/53785-9; Processo FAPESP: 10/20684-3; Processo FAPESP: 13/02018-4; Background: The apicomplexan parasite Neospora caninum causes neosporosis, a disease that leads to abortion or stillbirth in cattle, generating an economic impact on the dairy and beef cattle trade. As an obligatory intracellular parasite, N. caninum needs to invade the host cell in an active manner to survive. The increase in parasite cytosolic Ca2+ upon contact with the host cell mediates critical events, including the exocytosis of phylum-specific secretory organelles and the activation of the parasite invasion motor. Because invasion is considered a requirement for pathogen survival and replication within the host, the identification of secreted proteins (secretome) involved in invasion may be useful to reveal interesting targets for therapeutic intervention.Methods: To chart the currently missing N. caninum secretome, we employed mass spectrometry-based proteomics to identify proteins present in the N. caninum tachyzoite using two different approaches. The first approach was identifying the proteins present in the tachyzoite-secreted fraction (ESA). The second approach was determining the relative quantification through peptide stable isotope labelling of the tachyzoites submitted to an ethanol secretion stimulus (discharged tachyzoite)...

‣ The secretome of bone marrow mesenchymal stem cells-conditioned media varies with time and drives a distinct effect on mature neurons and glial cells (primary cultures)

Ribeiro, Carlos; Salgado, A. J.; Fraga, J. S.; Silva, Nuno; Reis, R. L.; Sousa, Nuno
Fonte: Wiley Publicador: Wiley
Tipo: Artigo de Revista Científica
Publicado em /01/2011 Português
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Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been shown to ameliorate the injured central nervous system (CNS). Although these effects were initially attributed to the putative differentiation of MSCs towards the neural lineage, it is now known that most of them are mediated by the secretome. Up to now most in vitro reports have dealt with the effects of the secretome on neural stem cells and their differentiation. Consequently, there is a lack of information regarding the role of the secretome on the viability and survival of pre-existent matured differentiated cell populations. Moreover, it is also not known how the time points of conditioned media (CM) collection affect such parameters. In the present study, primary cultures of hippocampal neurons and glial cells were incubated with CM obtained from MSCs. To determine how the temporal profiles of CM collection impact on post-natal neurons and glial cells, we collected MSCs CM at 24, 48, 72 and 96 h of conditioning. MTS test revealed that for the hippocampal cultures the incubation with CM increased cell viability for all time points, with significant increases in the percentage of neurons in culture incubated with CM 24 h. For glial cells only the later time point of CM collection (96 h) increased cell viability. Fluorescence microscopy observations also revealed that CM 48 h and 72 h increased astrocytes percentages...

‣ Adipose tissue derived stem cells secretome : soluble factors and their roles in regenerative medicine

Salgado, A. J.; Reis, R. L.; Sousa, Nuno; Gimble, Jeffrey M.
Fonte: Bentham Science Publishers Publicador: Bentham Science Publishers
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of a variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs’ secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF)...

‣ The secretome of stem cells isolated from the adipose tissue and wharton jelly acts differently on central nervous system derived cell populations

Ribeiro, Carlos A.; Fraga, J. S.; Grãos, Mário; Neves, N. M.; Reis, R. L.; Sousa, Nuno; Salgado, A. J.; Gimble, Jeffrey M.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em /05/2012 Português
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Introduction: It is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate the inured CNS. However it is still not clear whether they have similar or opposite effects on primary cultures of neuronal populations. The objective of the present work was to determine if ASCs and HUCPVCs preferentially act, or not, on specific cell populations within the CNS. Methods: Primary cultures of hippocampal neurons were exposed to ASCs and HUCPVCs conditioned media (CM) (obtained 24, 48, 72 and 96 hours after 3 days of culture) for 1 week. Results: Cell viability experiments (MTS test) revealed that CM obtained from both cell populations at all time points did not cause any deleterious effects on neuronal cells. In fact, it was determined that whenever the ASCs CM were supplemented with bFGF and B27, there was a significant increase on the metabolic viability and neuronal cell density of the cultures. On the other hand in the absence of CM supplementation, it was the HUCPVCs secretome that had the highest impact on the metabolic viability and cell density. In an attempt to unveil which factors could be involved in the observed effects, a screening for the presence of basic fibroblast growth factor (bFGF)...

‣ Secretome analysis of Ashbya gossypii

Aguiar, Tatiana Quinta; Penttilä, Merja; Domingues, Lucília
Fonte: Universidade do Minho Publicador: Universidade do Minho
Tipo: Conferência ou Objeto de Conferência
Publicado em //2010 Português
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To explore the potential Ashbya gossypii extracellular secretome two computational protocols were used. The 4726 protein-encoding genes predicted in the genome of A. gossypii strain ATCC 10895 were the data source for the analysis. Depending on the computational methods used, 171 to 185 proteins were predicted to be secreted proteins. Based on the results of the present study, A. gossypii is more similar to the closely related yeast Saccharomyces cerevisiae than to other filamentous fungi in its secretion ability.

‣ Modulation of bone marrow mesenchymal stem cell secretome by ECM-like hydrogels

Silva, N. A.; Moreira, Joana; Samy, Silvina Maria Ribeiro; Gomes, Eduardo D.; Tam, Roger Y.; Shoichet, Molly S.; Reis, R. L.; Sousa, Nuno; Salgado, A. J.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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It has been demonstrated that bone marrow mesenchymal stem cell (BM-MSCs) transplantation has beneficial effects on several central nervous system (CNS) debilitating conditions. Growing evidence indicate that trophic factors secreted by these cells are the key mechanism by which they are acting. These cells are frequently used in combination with 3D artificial matrices, for instance hydrogels, in tissue engineering-based approaches. However, so far, no study has been reported on the influence of such matrices, namely the presence or absence of extracellular matrix motifs, on BM-MSCs secretome and its effects in neuronal cell populations. In this sense, we herein studied the impact of a hydrogel, gellan gum, on the behavior and secretome of BM-MSCs, both in its commercial available form (commonly used in tissue engineering) and in a fibronectin peptide-modified form. The results showed that in the presence of a peptide in the gellan gum hydrogel, BM-MSCs presented higher proliferation and metabolic activity than in the regular hydrogel. Moreover, the typical spindle shape morphology of BM-MSCs was only observed in the modified hydrogel. The effects of the secretome of BM-MSCs were also affected by the chemical nature of the extracellular matrix. BM-MSCs cultured in the modified hydrogel were able to secrete factors that induced higher metabolic viabilities and neuronal cell densities...

‣ The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection

van Ooij, Christiaan; Tamez, Pamela; Bhattacharjee, Souvik; Hiller, N. Luisa; Harrison, Travis; Liolios, Konstantinos; Kooij, Taco; Ramesar, Jai; Balu, Bharath; Adams, John; Waters, Andy; Janse, Chris; Haldar, Kasturi
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful...

‣ The cancer secretome: a reservoir of biomarkers

Xue, Hua; Lu, Bingjian; Lai, Maode
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 17/09/2008 Português
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Biomarkers are pivotal for cancer detection, diagnosis, prognosis and therapeutic monitoring. However, currently available cancer biomarkers have the disadvantage of lacking specificity and/or sensitivity. Developing effective cancer biomarkers becomes a pressing and permanent need. The cancer secretome, the totality of proteins released by cancer cells or tissues, provides useful tools for the discovery of novel biomarkers. The focus of this article is to review the recent advances in cancer secretome analysis. We aim to elaborate the approaches currently employed for cancer secretome studies, as well as its applications in the identification of biomarkers and the clarification of carcinogenesis mechanisms. Challenges encountered in this newly emerging field, including sample preparation, in vivo secretome analysis and biomarker validation, are also discussed. Further improvements on strategies and technologies will continue to drive forward cancer secretome research and enable development of a wealth of clinically valuable cancer biomarkers.

‣ In Vivo Tumor Secretion Probing Via Ultrafiltration and Tissue Chamber: Implication for Anti-Cancer Drugs Targeting Secretome

Huang, Chun-Ming; Nakatsuji, Teruaki; Liu, Yu-Tseung; Shi, Yang
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2008 Português
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Tumor secreted proteins/peptides (tumor secretome) act as mediators of tumor-host communication in the tumor microenvironment. Therefore, development of anti-cancer drugs targeting secretome may effectively control tumor progression. Novel techniques including a capillary ultrafiltration (CUF) probe and a dermis-based cell-trapped system (DBCTS) linked to a tissue chamber were utilized to sample in vivo secretome from tumor masses and microenvironments. The CUF probe and tissue chamber were evaluated in the context of in vivo secretome sampling. Both techniques have been successfully integrated with mass spectrometry for secretome identification. A secretome containing multiple proteins and peptides can be analyzed by NanoLC-LTQ mass spectrometry, which is specially suited to identifying proteins in a complex mixture. In the future, the establishment of comprehensive proteomes of various host and tumor cells, as well as plasma will help in distinguishing the cellular sources of secretome. Many detection methods have been patented regarding probes and peptide used for identification of tumors.

‣ Secretome From Mesenchymal Stem Cells Induces Angiogenesis Via Cyr61

ESTRADA, ROSENDO; LI, NA; SAROJINI, HARSHINI; AN, JIN; LEE, MENQ-JER; WANG, EUGENIA
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/2009 Português
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It is well known that bone marrow-derived mesenchymal stem cells (MSCs) are involved in wound healing and regeneration responses. In this study, we globally profiled the proteome of MSCs to investigate critical factor(s) that may promote wound healing. Cysteine-rich protein 61 (Cyr61) was found to be abundantly present in MSCs. The presence of Cyr61 was confirmed by immunofluorescence staining and immunoblot analysis. Moreover, we showed that Cyr61 is present in the culture medium (secretome) of MSCs. The secretome of MSCs stimulates angiogenic response in vitro, and neovascularization in vivo. Depletion of Cyr61 completely abrogates the angiogenic-inducing capability of the MSC secretome. Importantly, addition of recombinant Cyr61 polypeptides restores the angiogenic activity of Cyr61-depleted secretome. Collectively, these data demonstrate that Cyr61 polypeptide in MSC secretome contributes to the angiogenesis-promoting activity, a key event needed for regeneration and repair of injured tissues.

‣ Senescent cells develop a PARP-1 and nuclear factor-κB-associated secretome (PNAS)

Ohanna, Mickaël; Giuliano, Sandy; Bonet, Caroline; Imbert, Véronique; Hofman, Véronique; Zangari, Joséphine; Bille, Karine; Robert, Caroline; Bressac-de Paillerets, Brigitte; Hofman, Paul; Rocchi, Stéphane; Peyron, Jean-François; Lacour, Jean-Philip
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em 15/06/2011 Português
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Melanoma cells can enter the process of senescence, but whether they express a secretory phenotype, as reported for other cells, is undetermined. This is of paramount importance, because this secretome can alter the tumor microenvironment and the response to chemotherapeutic drugs. More generally, the molecular events involved in formation of the senescent-associated secretome have yet to be determined. We reveal here that melanoma cells experiencing senescence in response to diverse stimuli, including anti-melanoma drugs, produce an inflammatory secretory profile, where the chemokine ligand-2 (CCL2) acts as a critical effector. Thus, we reveal how senescence induction might be involved in therapeutic failure in melanoma. We further provide a molecular relationship between senescence induction and secretome formation by revealing that the poly(ADP-ribose) polymerase-1 (PARP-1)/nuclear factor-κB (NF-κB) signaling cascade, activated during senescence, drives the formation of a secretome endowed with protumoral and prometastatic properties. Our findings also point to the existence of the PARP-1 and NF-κB-associated secretome, termed the PNAS, in nonmelanoma cells. Most importantly, inhibition of PARP-1 or NF-κB prevents the proinvasive properties of the secretome. Collectively...

‣ Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease

Ranganath, Sudhir H.; Levy, Oren; Inamdar, Maneesha S.; Karp, Jeffrey M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 02/03/2012 Português
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The broad repertoire of secreted trophic and immunomodulatory cytokines produced by mesenchymal stem cells (MSCs), generally referred to as the MSC secretome, has considerable potential for the treatment of cardiovascular disease. However, harnessing this MSC secretome towards meaningful therapeutic outcomes is challenging due to limited control on cytokine production following transplantation. This review outlines current understanding of the MSC secretome as a therapeutic for treatment of ischemic heart disease. We discuss ongoing investigative directions aimed at improving cellular activity and characterizing the secretome and its regulation in greater detail. Finally, we provide insights and perspectives for future development of the MSC secretome as a therapeutic tool.

‣ The human secretome atlas initiative: Implications in health and disease conditions

Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J.; Rose, Mary C; Hathout, Yetrib
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts towards secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study.

‣ HCSD: the human cancer secretome database

Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 13/06/2015 Português
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The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology. The secreted proteins from cancer cells are believed to play a deterministic role in cancer progression and therefore may be the key to find novel therapeutic targets and biomarkers for many cancers. Consequently, huge data on cancer secretome have been generated in recent years and the lack of a coherent database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein.

‣ Mutant p53 uses p63 as a molecular chaperone to alter gene expression and induce a pro-invasive secretome

Neilsen, P.; Noll, J.; Suetani, R.; Schulz, R.; Al-ejeh, F.; Evdokiou, A.; Lane, D.; Callen, D.
Fonte: Impact Journals LLC Publicador: Impact Journals LLC
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Mutations in the TP53 gene commonly result in the expression of a full-length protein that drives cancer cell invasion and metastasis. Herein, we have deciphered the global landscape of transcriptional regulation by mutant p53 through the application of a panel of isogenic H1299 derivatives with inducible expression of several common cancer-associated p53 mutants. We found that the ability of mutant p53 to alter the transcriptional profile of cancer cells is remarkably conserved across different p53 mutants. The mutant p53 transcriptional landscape was nested within a small subset of wild-type p53 responsive genes, suggesting that the oncogenic properties of mutant p53 are conferred by retaining its ability to regulate a defined set of p53 target genes. These mutant p53 target genes were shown to converge upon a p63 signalling axis. Both mutant p53 and wild-type p63 were co-recruited to the promoters of these target genes, thus providing a molecular basis for their selective regulation by mutant p53. We demonstrate that mutant p53 manipulates the gene expression pattern of cancer cells to facilitate invasion through the release of a pro-invasive secretome into the tumor microenvironment. Collectively, this study provides mechanistic insight into the complex nature of transcriptional regulation by mutant p53 and implicates a role for tumor-derived p53 mutations in the manipulation of the cancer cell secretome.; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282078/; Paul M. Neilsen...

‣ The secretome in cancer progression

Paltridge, J.; Belle, L.; Khew-Goodall, Y.
Fonte: Elsevier Science BV Publicador: Elsevier Science BV
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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The secretome is the collection of all macromolecules secreted by a cell, and is a vital aspect of cell-cell communication in eukaryotes. In cancer, tumour cells often display secretomes with altered composition compared to the normal tissue from which they are derived. These changes can contribute to the acquisition and maintenance of the recognised hallmarks of cancer. In addition, evidence is emerging for a more sophisticated role for the tumour secretome in cancer, with significant implications for malignant disease progression. In this review, we highlight recent advances in our understanding of factors contributing to secretome alterations in cancer, including genetic mutations, microRNA-based regulation and the influence of the tumour microenvironment. The contribution of secreted factors in maintenance and function of cancer stem cells, and of tumour-derived factors in specification of a pre-metastatic niche are also discussed. Collectively, evidence from the current literature suggests that the tumour secretome, consisting of factors derived from cancer stem cells, non-stem cells and the surrounding stroma, plays a deterministic role in cancer progression, and may constitute a key therapeutic target in many cancers. This article is part of a Special Issue entitled: An Updated Secretome.; James L. Paltridge...

‣ Vassoura-de-bruxa : caracterização de um metanol oxidase extracelular e do secretoma de Moniliophthora perniciosa; Witche¿s broom disease : characterization of an extracellular methanol oxidase and of the secretome of Moniliophthora perniciosa

Bruno Vaz de Oliveira
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 30/08/2012 Português
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O fungo basidiomiceto Moniliophthora perniciosa é o agente causador da vassoura-de-bruxa do cacaueiro, doença que se tornou um dos principais problemas fitopatológicos do Brasil. O fungo possui duas fases de vida, biotrófica e necrotrófica, as quais estão associadas aos sintomas de vassoura-verde e vassoura-seca, respectivamente, durante a progressão da doença. Em vista dos grandes prejuízos econômicos causados pela vassoura-de-bruxa, foi iniciado o Projeto Genoma Vassoura-de-Bruxa, cujo objetivo é a decodificação genética do fungo com o intuito de identificar genes candidatos que possam estar relacionados ao estabelecimento e à progressão da doença para serem caracterizados. M. perniciosa é capaz de utilizar metanol como fonte única de carbono. Na maioria dos organismos estudados, a enzima metanol oxidase (MOX) é a responsável pelo metabolismo de metanol através do metabolismo peroxissomal, à qual também está associada uma catalase (CAT). Em plantas, uma das principais fontes de metanol é a pectina presente na estrutura da parede celular vegetal. Algumas espécies de fungos fitopatogênicos tem a capacidade de secretar oxalato como produto da enzima oxaloacetato acetilhidrolase (OAH), o qual é capaz de quelar íons cálcio da estrutura das pectinas...

‣ Mesenchymal stem cells in the umbilical cord : phenotypic characterization, secretome and applications in central nervous system regenerative medicine

Carvalho, Miguel; Teixeira, Fábio; Sousa, Nuno; Salgado, A. J.
Fonte: Bentham Science Publishers Publicador: Bentham Science Publishers
Tipo: Artigo de Revista Científica
Publicado em /09/2011 Português
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Mesenchymal Stem Cells (MSCs), have been defined and characterized by: 1) their ability to adhere to plastic culture flasks; 2) the positive expression of CD105, CD73, CD90 membrane antigens, and the lack of expression of others (e.g CD45 and CD34) and 3) the ability of differentiation under adequate conditions along the osteogenic, chondrogenic and adipogenic lineages. In recent years, cells with these characteristics have been isolated from the Wharton’s jelly of the Umbilical Cord (UC). Similarly to bone marrow MSCs, they have shown multilineage differentiation potential and to be able to provide trophic support to neighboring cells. According to the literature, there are two main populations of cells with a mesenchymal character within the human UC: Wharton's jelly Mesenchymal Stem Cells (WJ-MSCs) and Human Umbilical Cord Perivascular Cells (HUCPVCs). In the present work our aim is to make a comprehensive review on MSC populations of the UC and how these cell populations may be used for future applications in CNS regenerative medicine. Following a brief insight on the general characteristics of MSC like cells, we will discuss the possible sources of stem cells within the WJ and the cord itself (apart UC blood), as well as their phenotypic character. As it has already been shown that these cells hold a strong trophic support to neighbouring cell populations...