Conditioned media from cell lines: A complementary model to clinical specimens for the discovery of disease‐specific biomarkers

Abstract

In the strictest sense, the cell secretome (conditioned media) refers to the collection of proteins that contain a signal peptide and are processed via the endoplasmic reticulum and Golgi apparatus through the classical secretion pathway. More generally, the secretome also encompasses proteins shed from the cell surface and intracellular proteins released through non-classical secretion pathway or exosomes. These secreted proteins include numerous enzymes, growth factors, cytokines and hormones or other soluble mediators. They are fundamental in the processes of cell growth, differentiation, invasion and angiogenesis by regulating cell-to-cell and cell-to-extracellular matrix interactions. The main aim of this review is to provide a synopsis of findings from the analysis of the secretome taking diabetes, cancer and neurodegenerative diseases as examples. We will also discuss the preparation of conditioned media and on the main proteomic-based methodological approaches that have been developed for the study of secreted/shed proteins.

Identification of secreted proteins that reflect autophagy dynamics within tumor cells

“…Taken together, 38% of the differentially secreted proteins reside in the extracellular matrix, cell surface, or plasma membrane, the most common localizations previously identified for nonclassically secreted proteins. 23 Nonclassically secreted proteins also include cytokines, hormones, and growth factors that regulate cell growth, differentiation, invasion, and angiogenesis, 24 cell processes that represented 27% of the biological process GO terms derived from our secretome when including immune-related, developmental, and stimulus response processes (Fig. 2C).…”

Systematic Proteomic Analysis Identifies β-Site Amyloid Precursor Protein Cleaving Enzyme 2 and 1 (BACE2 and BACE1) Substrates in Pancreatic β-Cells

“…Proteomic Mapping of the ␤-Cell Secretome and SheddomeThe analysis of proteins released in the media of cell lines or primary cultures is a powerful tool to identify biologically active peptides and facilitate their evaluation as biomarker for cancer, neurodegenerative diseases and diabetes (32). We have employed the technique to estimate the fraction of the sheddome that is regulated by BACE2 and BACE1, but also to explore the global secretome and sheddome of MIN6 cells and , BACE DKO) and wildtype controls and of wildtype islets that were cultured in the presence of 100 nmol/l BACE2 inhibitor compound J (CpdJ) or its vehicle DMSO were analyzed by SRM/MRM mass spectrometry.…”

Analytical constraints for the analysis of human cell line secretomes by shotgun proteomics

“…It reflects the cellular state of cells as the quantity of secreted proteins may vary depending on the stimuli they received. Secreted proteins play a crucial role in many physiological processes [1]. They include numerous growth factors, cytokines, hormones, and enzymes.…”