Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer.

Background: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.

Results: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics.

RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed.

Embryonic protein NODAL regulates the breast tumor microenvironment by reprogramming cancer-derived secretomes.

The tumor microenvironment (TME) is an important mediator of breast cancer progression. Cancer-associated fibroblasts constitute a major component of the TME and may originate from tissue-associated fibroblasts or infiltrating mesenchymal stromal cells (MSCs). The mechanisms by which cancer cells activate fibroblasts and recruit MSCs to the TME are largely unknown, but likely include deposition of a pro-tumorigenic secretome.

ADAM protease inhibition overcomes resistance of breast cancer stem-like cells to γδ T cell immunotherapy.

Gamma delta T cells (γδTc) have tremendous anti-tumoral activity, thus γδTc immunotherapy is currently under development for various malignancies. We targeted breast cancer stem-like cells (BCSC), a rare cell population responsible for patient mortality. BCSC were mostly susceptible to γδTc immunotherapy, yet some escaped.

Translational control of breast cancer plasticity.

Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast cancer cells NANOG, SNAIL and NODAL transcripts manifest multiple isoforms characterized by different 5' Untranslated Regions (5'UTRs), whereby translation of a subset of these isoforms is stimulated under hypoxia. The accumulation of the corresponding proteins induces plasticity and "fate-switching" toward stem cell-like phenotypes.

Proteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma.

Purpose: Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches.

Experimental Design: To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, = 10; endometrioid carcinoma, = 10).

Comparison of sample preparation techniques for large-scale proteomics.

Numerous workflows exist for large-scale bottom-up proteomics, many of which achieve exceptional proteome depth. Herein, we evaluated the performance of several commonly used sample preparation techniques for proteomic characterization of HeLa lysates [unfractionated in-solution digests, SDS-PAGE coupled with in-gel digestion, gel-eluted liquid fraction entrapment electrophoresis (GELFrEE) technology, SCX StageTips and high-/low-pH reversed phase fractionation (HpH)]. HpH fractionation was found to be superior in terms of proteome depth (>8400 proteins detected) and fractionation efficiency compared to other techniques.

Embryonic morphogen nodal promotes breast cancer growth and progression.

Breast cancers expressing human embryonic stem cell (hESC)-associated genes are more likely to progress than well-differentiated cancers and are thus associated with poor patient prognosis. Elevated proliferation and evasion of growth control are similarly associated with disease progression, and are classical hallmarks of cancer. In the current study we demonstrate that the hESC-associated factor Nodal promotes breast cancer growth.

Low oxygen levels induce the expression of the embryonic morphogen Nodal.

Low oxygen (O(2)) levels characterize the microenvironment of both stem cells and rapidly growing tumors. Moreover, hypoxia is associated with the maintenance of stem cell-like phenotypes and increased invasion, angiogenesis and metastasis in cancer patients. Metastatic cancers, such as breast cancer and melanoma, aberrantly express the embryonic morphogen Nodal, and the presence of this protein is correlated with metastatic disease.