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At least 19 recordsLinked to original sources
PubMed2026

Prolonged In Vitro Expansion Shapes the Neuro-Supportive Potential of Jaw Periosteum Secretomes: Implications for Secretome Product Quality.

Nerve injuries are frequent complications of complex oral and maxillofacial surgical procedures, particularly following extensive tumor resections. Secretome-based, cell-free therapies derived from mesenchymal stromal cells have emerged as promising regenerative approaches; however, robust manufacturing requires the identification of critical quality attributes (CQAs) that ensure product potency and consistency. The influence of replicative senescence during in vitro expansion on the quality of jaw periosteum-derived mesenchymal stromal cell (JPC) secretomes has not yet been established. This study investigated whether the expansion state of JPCs affects the composition and neuro-supportive potency of their secretomes. Secretomes from four independent JPC donors were collected separately at early and late passages, pooled within each passage-specific preparation, and applied to human induced pluripotent stem cell-derived neurons. Neuronal survival, neurite outgrowth, and neuronal marker expression were assessed as functional readouts. Secretome composition was characterized by quantitative proteomics and enzyme-linked immunosorbent assay (ELISA) of selected senescence-associated secretory phenotype (SASP) factors. Secretomes derived from early-passage JPCs significantly enhanced neuronal survival and neurite outgrowth, whereas late-passage secretomes displayed reduced neuro-supportive activity. Proteomic profiling identified a pronounced shift toward inflammatory and stress-associated signaling, whereas performed ELISAs confirmed senescence-associated remodeling of the secretome, including increased abundance of SASP-associated factors in late-passage preparations. These findings demonstrate that prolonged in vitro expansion profoundly influences both the composition and biological potency of JPC-derived secretomes. Collectively, this study identifies the passage-associated senescence-like phenotype of JPCs as a key determinant of secretome quality and supports its consideration as a critical quality attribute for the manufacturing and standardization of JPC-derived secretome products. Monitoring and controlling the expansion state of JPCs may therefore be essential to ensure the consistency, potency, and clinical translation of secretome-based regenerative therapies.

Humans↗
PubMed2006

Mapping the pathways to staphylococcal pathogenesis by comparative secretomics.

The gram-positive bacterium Staphylococcus aureus is a frequent component of the human microbial flora that can turn into a dangerous pathogen. As such, this organism is capable of infecting almost every tissue and organ system in the human body. It does so by actively exporting a variety of virulence factors to the cell surface and extracellular milieu. Upon reaching their respective destinations, these virulence factors have pivotal roles in the colonization and subversion of the human host. It is therefore of major importance to obtain a clear understanding of the protein transport pathways that are active in S. aureus. The present review aims to provide a state-of-the-art roadmap of staphylococcal secretomes, which include both protein transport pathways and the extracytoplasmic proteins of these organisms. Specifically, an overview is presented of the exported virulence factors, pathways for protein transport, signals for cellular protein retention or secretion, and the exoproteomes of different S. aureus isolates. The focus is on S. aureus, but comparisons with Staphylococcus epidermidis and other gram-positive bacteria, such as Bacillus subtilis, are included where appropriate. Importantly, the results of genomic and proteomic studies on S. aureus secretomes are integrated through a comparative "secretomics" approach, resulting in the first definition of the core and variant secretomes of this bacterium. While the core secretome seems to be largely employed for general housekeeping functions which are necessary to thrive in particular niches provided by the human host, the variant secretome seems to contain the "gadgets" that S. aureus needs to conquer these well-protected niches.

Bacterial Proteins↗
PubMed2025

An atlas of ferroptosis-induced secretomes.

Cells undergoing regulated necrosis systemically communicate with the immune system via the release of protein and non-protein secretomes. Ferroptosis is a recently described iron-dependent type of regulated necrosis driven by massive lipid peroxidation. While membrane rupture occurs during ferroptosis, a comprehensive appraisal of ferroptotic secretomes and their potential biological activity has been lacking. Here, we apply a multi-omics approach to provide an atlas of ferroptosis-induced secretomes and reveal a novel function in macrophage priming. Proteins with assigned DAMP and innate immune system function, such as MIF, heat shock proteins (HSPs), and chaperones, were released from ferroptotic cells. Non-protein secretomes with assigned inflammatory function contained oxylipins as well as TCA- and methionine-cycle metabolites. Interestingly, incubation of bone marrow-derived macrophages (BMDMs) with ferroptotic supernatants induced transcriptional reprogramming consistent with priming. Indeed, exposure to ferroptotic supernatants enhanced LPS-induced cytokine production. These results define a catalog of ferroptosis-induced secretomes and identify a biological activity in macrophage priming with important implications for the fine-tuning of inflammatory processes.

Ferroptosis↗
PubMed2024

Secretome Analysis Using Affinity Proteomics and Immunoassays: A Focus on Tumor Biology.

The study of the cellular secretome using proteomic techniques continues to capture the attention of the research community across a broad range of topics in biomedical research. Due to their untargeted nature, independence from the model system used, historically superior depth of analysis, as well as comparative affordability, mass spectrometry-based approaches traditionally dominate such analyses. More recently, however, affinity-based proteomic assays have massively gained in analytical depth, which together with their high sensitivity, dynamic range coverage as well as high throughput capabilities render them exquisitely suited to secretome analysis. In this review, we revisit the analytical challenges implied by secretomics and provide an overview of affinity-based proteomic platforms currently available for such analyses, using the study of the tumor secretome as an example for basic and translational research.

Humans↗
PubMed2006

Mass spectrometric proteomics profiles of in vivo tumor secretomes: capillary ultrafiltration sampling of regressive tumor masses.

Identification of in vivo secreted peptides/proteins (secretomes) in tumor masses has the potential to provide important biomarkers and therapeutic targets for cancer therapy. However, limitations of existing technologies have made obtaining these secretomes for analysis extremely difficult. Here we employed an in vivo sampling technique using capillary ultrafiltration (CUF) probes to collect secretomes directly from tumor masses. Mass spectrometric proteomics approaches were then used to identify the tumor secretomes. A UV-induced skin fibrosarcoma cell line (UV-2240) was subcutaneously injected into C3H/NeH mice, resulting in tumor masses that initially progressed, then regressed and eventually eradicated. We then implanted CUF probes into tumor masses at the progressive and regressive stage. Five secreted proteins (cyclophilin-A, S100A4, profilin-1, thymosin beta 4 and 10), previously associated with tumor progression, were identified from tumor masses at the progressive stage. Five secreted proteins including three protease inhibitors (fetuin-A, alpha-1 antitrypsin 1-6, and contrapsin) were identified from tumor masses at the regressive stage. The technique involving CUF probes linked to mass spectrometric proteomics reinforces systems biology studies of cell-cell interactions and is potentially applicable to the discovery of in vivo biomarkers in human disease.

Animals↗
PubMed2006

Analysis of protein expression (secretome) by human and mouse preimplantation embryos.

OBJECTIVE: To analyze the protein production into the surrounding medium (secretome) of both human and mouse embryos and correlate these findings with ongoing blastocyst development. Along with improvements in culture systems, there is renewed focus on the development of noninvasive viability assays in human IVF. Because the majority of biologic functions are carried out by proteins, it is important to study the dynamics of the proteome during embryonic development and its response to both internal and external stimuli. DESIGN: Experimental study. SETTING: Research laboratory. PATIENT(S): Couples undergoing infertility treatment donated with consent spent culture media for research. INTERVENTION(S): Analysis by time-of-flight mass spectrometry. MAIN OUTCOME MEASURE(S): Protein profiles of spent culture media. RESULT(S): Distinctive and significantly different secretome profiles were observed at each embryonic developmental stage (P<0.05). Correlation of day 5 secretome data with ongoing blastocyst development revealed an 8.5-kDa protein biomarker that was significantly up-regulated (P<0.05). The best candidate for this protein biomarker was ubiquitin, which has been implicated in the implantation process of mammalian species. CONCLUSION(S): This approach to analyze the secretome should not only further our understanding of embryo physiology but provide the basis for the development of noninvasive assays of embryo viability in human IVF.

Animals↗
PubMed2006

A rapidly evolving secretome builds and patterns a sea shell.

BACKGROUND: Instructions to fabricate mineralized structures with distinct nanoscale architectures, such as seashells and coral and vertebrate skeletons, are encoded in the genomes of a wide variety of animals. In mollusks, the mantle is responsible for the extracellular production of the shell, directing the ordered biomineralization of CaCO3 and the deposition of architectural and color patterns. The evolutionary origins of the ability to synthesize calcified structures across various metazoan taxa remain obscure, with only a small number of protein families identified from molluskan shells. The recent sequencing of a wide range of metazoan genomes coupled with the analysis of gene expression in non-model animals has allowed us to investigate the evolution and process of biomineralization in gastropod mollusks. RESULTS: Here we show that over 25% of the genes expressed in the mantle of the vetigastropod Haliotis asinina encode secreted proteins, indicating that hundreds of proteins are likely to be contributing to shell fabrication and patterning. Almost 85% of the secretome encodes novel proteins; remarkably, only 19% of these have identifiable homologues in the full genome of the patellogastropod Lottia scutum. The spatial expression profiles of mantle genes that belong to the secretome is restricted to discrete mantle zones, with each zone responsible for the fabrication of one of the structural layers of the shell. Patterned expression of a subset of genes along the length of the mantle is indicative of roles in shell ornamentation. For example, Has-sometsuke maps precisely to pigmentation patterns in the shell, providing the first case of a gene product to be involved in molluskan shell pigmentation. We also describe the expression of two novel genes involved in nacre (mother of pearl) deposition. CONCLUSION: The unexpected complexity and evolvability of this secretome and the modular design of the molluskan mantle enables diversification of shell strength and design, and as such must contribute to the variety of adaptive architectures and colors found in mollusk shells. The composition of this novel mantle-specific secretome suggests that there are significant molecular differences in the ways in which gastropods synthesize their shells.

Animal Structures↗
PubMed2024

Value of a secretomic approach for distinguishing patients with COVID-19 viral pneumonia among patients with respiratory distress admitted to intensive care unit.

In intensive care units, COVID-19 viral pneumonia patients (VPP) present symptoms similar to those of other patients with Nonviral infection (NV-ICU). To better manage VPP, it is therefore interesting to better understand the molecular pathophysiology of viral pneumonia and to search for biomarkers that may clarify the diagnosis. The secretome being a set of proteins secreted by cells in response to stimuli represents an opportunity to discover new biomarkers. The objective of this study is to identify the secretomic signatures of VPP with those of NV-ICU. Plasma samples and clinical data from NV-ICU (n&#x2009;=&#x2009;104), VPP (n&#x2009;=&#x2009;30) or healthy donors (HD, n&#x2009;=&#x2009;20) were collected at Nantes Hospital (France) upon admission. Samples were enriched for the low-abundant proteins and analyzed using nontarget mass spectrometry. Specifically deregulated proteins (DEP) in VPP versus NV-ICU were selected. Combinations of 2 to 4 DEPs were established. The differences in secretome profiles of the VPP and NV-ICU groups were highlighted. Forty-one DEPs were specifically identified in VPP compared to NV-ICU. We describe five of the best combinations of 3 proteins (complement component C9, Ficolin-3, Galectin-3-binding protein, Fibrinogen alpha, gamma and beta chain, Proteoglycan 4, Coagulation factor IX and Cdc42 effector protein 4) that show a characteristic receptor function curve with an area under the curve of 95.0%. This study identifies five combinations of candidate biomarkers in VPP compared to NV-ICU that may help distinguish the underlying causal molecular alterations.

Humans↗
PubMed2006

Definition and spatial annotation of the dynamic secretome during early kidney development.

The term "secretome" has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350-1359). The term "secreted protein" encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.

Animals↗
PubMed2006

Secretome of primary cultures of human adipose-derived stem cells: modulation of serpins by adipogenesis.

Studies of adipogenic protein induction have led to a new appreciation of the role of adipose tissue as an endocrine organ. Adipocyte-derived "adipokines" such as adiponectin, leptin, and visceral adipose tissue-derived serine protease inhibitor (vaspin) exert hormone-like activities at the systemic level. In this study, we examined the secretome of primary cultures of human subcutaneous adipose-derived stem cells as an in vitro model of adipogenesis. Conditioned media obtained from four individual female donors after culture in uninduced or adipogenic induced conditions were compared by two-dimensional gel electrophoresis and tandem mass spectrometry. Over 80 individual protein features showing > or =2-fold relative differences were examined. Approximately 50% of the identified proteins have been described previously in the secretome of murine 3T3-L1 preadipocytes or in the interstitial fluid derived from human mammary gland adipose tissue. As reported by others, we found that the secretome included proteins such as actin and lactate dehydrogenase that do not display a leader sequence or transmembrane domain and are classified as "cytoplasmic" in origin. Moreover we detected a number of established adipokines such as adiponectin and plasminogen activator inhibitor 1. Of particular interest was the presence of multiple serine protease inhibitors (serpins). In addition to plasminogen activator inhibitor 1, these included pigment epithelium-derived factor (confirmed by Western immunoblot), placental thrombin inhibitor, pregnancy zone protein, and protease C1 inhibitor. These findings, together with the recent identification of vaspin, suggest that the serpin protein family warrants further proteomics investigation with respect to the etiology of obesity and type 2 diabetes.

3T3-L1 Cells↗
PubMed2006

A functional screen to characterize the secretomes of eukaryotic pathogens and their hosts in planta.

Complex suites of proteins that are secreted by plants and phytopathogens into the plant apoplast play crucial roles in surveillance, assault, defense, and counter-defense. High-throughput genome-scale strategies are being developed to better understand the nature of these "secretomes" and the identity of pathogen-derived effector proteins that subvert plant defenses and promote pathogenicity. Although combined bioinformatic and experimental approaches recently have provided comprehensive coverage of secreted proteins from bacterial phytopathogens, far less is known about the secretomes and batteries of effectors of eukaryotic phytopathogens; notably fungi and oomycetes. The yeast secretion trap (YST) represents a potentially valuable technique to simultaneously target pathogen and host secretomes in infected plant material. A YST screen, using a new vector system, was applied to study the interaction between tomato (Solanum lycopersicum) and the oomycete Phytophthora infestans, revealing sets of genes encoding secreted proteins from both pathogen and host. Most of those from the oomycete had no identifiable function and were detectable in planta only during pathogenesis, underlining the value of YST as a tool to identify new candidate effectors and pathogenicity factors. In addition, the majority of the P. infestans proteins had homologs in the genomes of the related oomycetes R. sojae and P. ramorum.

Algal Proteins↗
PubMed2006

Differential proteomic analysis of the Bacillus anthracis secretome: distinct plasmid and chromosome CO2-dependent cross talk mechanisms modulate extracellular proteolytic activities.

The secretomes of a virulent Bacillus anthracis strain and of avirulent strains (cured of the virulence plasmids pXO1 and pXO2), cultured in rich and minimal media, were studied by a comparative proteomic approach. More than 400 protein spots, representing the products of 64 genes, were identified, and a unique pattern of protein relative abundance with respect to the presence of the virulence plasmids was revealed. In minimal medium under high CO(2) tension, conditions considered to simulate those encountered in the host, the presence of the plasmids leads to enhanced expression of 12 chromosome-carried genes (10 of which could not be detected in the absence of the plasmids) in addition to expression of 5 pXO1-encoded proteins. Furthermore, under these conditions, the presence of the pXO1 and pXO2 plasmids leads to the repression of 14 chromosomal genes. On the other hand, in minimal aerobic medium not supplemented with CO(2), the virulent and avirulent B. anthracis strains manifest very similar protein signatures, and most strikingly, two proteins (the metalloproteases InhA1 and NprB, orthologs of gene products attributed to the Bacillus cereus group PlcR regulon) represent over 90% of the total secretome. Interestingly, of the 64 identified gene products, at least 31 harbor features characteristic of virulence determinants (such as toxins, proteases, nucleotidases, sulfatases, transporters, and detoxification factors), 22 of which are differentially regulated in a plasmid-dependent manner. The nature and the expression patterns of proteins in the various secretomes suggest that distinct CO(2)-responsive chromosome- and plasmid-encoded regulatory factors modulate the secretion of potential novel virulence factors, most of which are associated with extracellular proteolytic activities.

Amino Acid Sequence↗
PubMed2005

A novel technique to specifically analyze the secretome of cells and tissues.

The secretome of cells and tissues may reflect a broad variety of pathological conditions and thus represents a rich source of biomarkers. The identity of secreted proteins, usually isolated from cell supernatants or body fluids, is hardly accessible by direct proteome analysis, because these proteins are often masked by high amounts of proteins actually not secreted by the investigated cells. Here, we present a novel method for the specific detection of proteins secreted by human tissue specimen as well as cultured cells and chose liver as a model. The method is based on the metabolic labelling of proteins synthesized during a limited incubation period. Then, the cell supernatant is filtered, precipitated, and subjected to two-dimensional gel electrophoresis. Whereas fluorography detected a large number of proteins derived from residual plasma and dead cells, the autoradiographs selectively displayed genuinely secreted proteins. We demonstrate the feasibility of this approach by means of the secretomes of the hepatocellular carcinoma-derived cell line HepG2 and human liver slices. The selective identification of cell- and tissue-specific protein secretion profiles may help to identify novel sets of biomarkers for wide clinical applications.

Amino Acid Sequence↗
PubMed2004

Two-dimensional maps and databases of the human macrophage proteome and secretome.

Macrophages exert a crucial, but still incompletely known, role in complex disorders such inflammatory, immunological, and infectious diseases. A differential proteomic approach should help to elucidate the macrophage dysfunctions involved in these diseases. With this goal in mind, we established the first two-dimensional maps of the human macrophage proteome and secretome. Intracellular and secreted proteins were extracted from monocyte-derived macrophages obtained from healthy donors (n = 16), and separated by two-dimensional gel electrophoresis. Silver-stained gels were analyzed using Progenesis software. A high level of between-gel reproducibility was obtained, allowing us to generate two patterns specific of the macrophage proteome and secretome, respectively. A total of 127 and 66 distinct intracellular and secreted polypeptide spots, corresponding to 100 and 38 different proteins, respectively, were identified by matrix assisted laser desorption/ionisation-mass spectrometry. The two-dimensional reference maps and databases resulting from this study confirm that macrophages are involved in a wide range of biological functions, and that they provide a useful tool for a wide array of investigators involved in macrophage biology, allowing to investigate the macrophage protein changes associated with various disorders or environmental stimuli.

Databases, Protein↗
PubMed2004

Tumor suppressor Smad4 mediates downregulation of the anti-adhesive invasion-promoting matricellular protein SPARC: Landscaping activity of Smad4 as revealed by a "secretome" analysis.

We have demonstrated previously that restoration of Smad4 expression in Smad4-deficient SW480 human colon carcinoma cells was adequate to suppress tumorigenicity and invasive potential, whereas cell growth in vitro was not affected. Here we show that Smad4-positive and Smad4-negative SW480 cells deposit extracellular matrices in tissue culture which are functionally different with respect to their adhesiveness. We present a "differential secretomics analysis" as the most direct approach to identify the underlying alterations. The protein composition of conditioned media produced by Smad4-positive and Smad4-negative SW480 cells was compared by two-dimensional (2-D) gel electrophoresis. A major group of protein spots was detected in media derived from Smad4-negative cells, only, which were identified as "secreted protein, acidic and rich in cysteins" (SPARC) by mass spectrometry. SPARC expression in SW480 cells was suppressed by Smad4 at the level of transcription. SPARC is a glycoprotein of the extracellular matrix, characterized as an anti-adhesive and invasion-promoting protein. Differential secretomics appeared as a powerful method to identify a novel Smad4 target gene, which may be one of the players involved in reduced adhesiveness of extracellular matrices and thus consistent with Smad4's emerging role as an invasion suppressor.

Amino Acid Sequence↗
PubMed2005

The proteome and secretome of human arterial smooth muscle cells.

Smooth muscle cells (SMCs) play a crucial role in cardiovascular disorders. A differential proteomic approach should help to elucidate SMC dysfunctions involved in these diseases. With this goal in mind, we plotted the first 2-dimensional (2-D) maps of the proteome and secretome of human arterial smooth muscle cell (ASMC). Intracellular and secreted proteins were extracted from a primary culture of SMCs obtained from patients undergoing coronary artery bypass surgery (n = 11) and separated by 2-dimensional gel electrophoresis. Silver-stained gels were analyzed using Progenesis software. A high level of between-gel reproducibility was obtained, allowing us to generate two protein patterns specific to the ASMC proteome and secretome, respectively. A total of 121 and 40 distinct intracellular and secreted polypeptide spots, corresponding to 83 and 18 different proteins, respectively, were identified by matrix-assisted laser desorption/ionization mass spectrometry. The 2-D reference maps and database resulting from this study confirm that SMCs are involved in a wide range of biological functions. They could constitute a useful tool for a wide range of investigators involved in vascular biology, allowing them to investigate SMC protein changes associated with cardiovascular disorders or environmental stimuli.

Cells, Cultured↗
PubMed2006

Computational reconstruction of the human skeletal muscle secretome.

In multicellular organisms, secreted proteins play pivotal regulatory roles in intercellular communication. Proteins secreted by skeletal muscle can act locally on muscle cells through autocrine/paracrine loops and on surrounding tissues such as muscle blood vessels, or they can be released into the blood stream, thus producing systemic effects. By a computational approach, we have screened 6255 products of genes expressed in normal human skeletal muscle. Putatively secreted proteins were identified by sequential steps of sieving, through prediction of signal peptide, recognition of transmembrane regions, and analysis of protein annotation. The resulting putative skeletal muscle secretome consists of 319 proteins, including 78 still uncharacterized proteins. This is the first human skeletal muscle secretome produced by computational analysis. Knowledge of proteins secreted by skeletal muscle could stimulate development of novel treatments for different diseases, including muscle atrophy and dystrophy. In addition, better knowledge of the secretion process in skeletal muscle can be useful for future gene therapy approaches.

Animals↗
PubMed2005

Secretome analysis of microarray data reveals extracellular events associated with proliferative potential in a cell line model of breast disease.

It is widely believed that breast cancer develops in a multistep process with premalignant lesions preceding invasive carcinoma. The characterization of molecular events associated with premalignant progression would improve our understanding of carcinogenesis and greatly benefit the development of early detection methods and chemoprevention strategies. However, the molecular biology of precancerous breast disease is poorly understood. To better characterize extracellular events associated with disease progression, such as cell-cell and cell-extracellular matrix (ECM) signaling, we analyzed gene expression profiles for the set of genes coding for secreted proteins (the secretome) in a cell line model of human proliferative breast disease (PBD). PBD describes a series of preneoplastic changes in the inner lining of milk glands associated with a dramatic increase in the risk of breast cancer. We used a series of cell lines with increasing proliferative propensity, and cell cultures were grown on matrigel to emulate in vivo growth and ECM interactions. Microarray analysis identified two clusters of secretome genes with expression profiles correlating to PBD progression. Some of the identified genes have previously been associated with breast malignancies, and our results suggest that changes in expression for these genes begin in the premalignant stage, offering potential use for early detection and as chemotherapeutic targets. RT-PCR validation demonstrates the reliability of the microarray results.

Breast Neoplasms↗