The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context

Schaaij-Visser, Tieneke B.M.; Wit, Meike de; Lam, Siu W.; Jiménez, Connie R.

doi:10.1016/j.bbapap.2013.01.029

Cited by 94 publications

(81 citation statements)

References 111 publications

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“…Previous studies collectively demonstrate the utility of MPE proteomics in biomarker discovery for human cancers (8). The first proteomics study on MPE was published in 2004; in this study, Bard et al focused on identification of protein components derived from MPE exosomes in three cancer types (mesothelioma, lung, and breast cancer) by MALDI-TOF.…”

Section: Discussionmentioning

confidence: 99%

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In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 99%

“…Notably, tumor-proximal body fluids are promising sources for biomarker discovery because they represent a reservoir of in vivo tumor-secreted proteins without a large dynamic range or complexity of plasma or serum (8). Tumor-proximal fluids include PEs, nipple aspirate, stool, saliva, lavage, and ascites fluid.…”

mentioning

confidence: 99%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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“…Taken altogether, protein networks secreted by high AAI blasts appear to bear the potential to globally regulate expression of multiple apoptosis-related proteins at different levels. The presence of nuclear proteins in secretome is often assumed to be a contaminant and thereby may be frequently ignored; however, the functional implications of this phenomenon are currently emerging (48). In this respect, we recently identified an enrichment of nuclear proteins, including factors involved in splicing in secretomes derived from colorectal cancer tissues in comparison to healthy controls (49).…”

Section: Discussionmentioning

confidence: 90%

Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis

Wojtuszkiewicz

Schuurhuis

Kessler

et al. 2016

Molecular & Cellular Proteomics

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myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividual ex vivo apoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated. The expression values of apoptosisregulating proteins were far beyond healthy control lymphocytes, which implicates the influence of microenvironmental factors. Second, we demonstrated that apoptosis-resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p ‫؍‬ 0.0067 and p ‫؍‬ 1.0, respectively). Using secretome proteomics, we identified novel proteins possibly engaged in apoptosis regulation. Intriguingly, this analysis revealed that major functional protein clusters engaged in global gene regulation, including mRNA splicing, protein translation, and chromatin remodeling, were more abundant (p ‫؍‬ 4.01E-06) in secretomes of apoptosis-resistant AML. These findings were confirmed by subsequent extracellular vesicle proteomics. Despite good remission rates observed in acute myeloid leukemia (AML) patients, the 5-year event-free survival rates reach only 35-40% in adults and 60 -70% in children (1, 2). Apoptosis is one of the crucial mechanisms influencing survival of AML cells, and its deregulation can possibly lead to chemotherapy resistance and eventually relapse (3-5). The ability of cells to undergo apoptosis is largely defined by the relative expression of anti-(i.e. BCL-2, BCL-X long isoform -BCL-XL, or MCL-1) and proapoptotic (i.e. BAX, BH3 interacting domain death agonist -BID, caspases) proteins. Several studies have shown that the levels of BCL-2 and BCL-2/BAX ratio are a determinant of apoptosis-resistance in AML blasts and are associated with survival in AML patients (3,6). We have previously demonstrated that the expression of several apoptosis-related proteins, such as BCL-2, BCL-XL, MCL-1, From the ‡Dept.

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“…Currently, MVs from human nipple fluid and blood are considered as noninvasive sources of molecular biomarkers for early detection and prognosis of various types of cancers, including BC. 49 This approach is based on the content of MVs, and the molecular content of MVs is dependent on their cell origin and strongly associates with the original cellular conditions. For example, the concentration of MVs is significantly increased in the plasma of BC patients compared with healthy donors.…”

Section: Mvs As Diagnostic and Prognostic Bc Biomarkersmentioning

confidence: 99%

Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer

et al. 2017

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Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.

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The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context

Cited by 94 publications

References 111 publications

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis

Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer

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