Secretome Compartment Is a Valuable Source of Biomarkers for Cancer-Relevant Pathways

Abstract

In principle, targeted therapies have optimal activity against a specific subset of tumors that depend upon the targeted molecule or pathway for growth, survival, or metastasis. Consequently, it is important in drug development and clinical practice to have predictive biomarkers that can reliably identify patients who will benefit from a given therapy. We analyzed tumor cell-line secretomes (conditioned cell media) to look for predictive biomarkers; secretomes represent a potential source for potential biomarkers that are expressed in intracellular signaling and therefore may reflect changes induced by targeted therapy. Using Gene Ontology, we classified by function the secretome proteins of 12 tumor cell lines of different histotypes. Representations and hierarchical relationships among the functional groups differed among the cell lines. Using bioinformatics tools, we identified proteins involved in intracellular signaling pathways. For example, we found that secretome proteins related to TGF-beta signaling in thyroid cancer cells, such as vasorin, CD109, and βIG-H3 (TGFBI), were sensitive to RPI-1 and dasatinib treatments, which have been previously demonstrated to be effective in blocking cell proliferation. The secretome may be a valuable source of potential biomarkers for detecting cancer and measuring the effectiveness of cancer therapies.

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

“…As an example, the EX-CELL media are protein-free but contain the Pluronic F-68 polymer that can result concentrated along the procedure for secretome recovery. Finally, DMEM that was used for several secretome studies [2,14,21] appeared the best option as serum-free medium. Because its concentration of glucose (an essential carbon source for cellular catabolism) is high, a good viability was observed for BEAS-2B cells.…”

“…They include numerous growth factors, cytokines, hormones, and enzymes. In the recent years, they deserved much attention as among them are therapeutic targets or candidate diagnostic and prognosis biomarkers [2][3][4][5][6][7]. Technological advances in the proteomic field, such as the widespread use of new generation of high-resolution mass spectrometers and shotgun strategies, offer the possibility of identifying almost all proteins present in a given biological sample [8].…”

Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis

“…They reach target organs ahead of metastasis cancer cells and adapt the foreign tissues into a tumor-friendly environment that is called "metastasis niche" [12]. Overall, cancer cell secretome is a rich reservoir of biomarkers of cancer progression and molecular targets of cancer therapeutics, and thus is a topic of great interest for cancer research [5,13].…”

4-IPP, a selective MIF inhibitor, causes mitotic catastrophe in thyroid carcinomas

“…After 24 h, proteins secreted in the medium (secretome) by TPC-1 cells were collected and identified, as previously described (Caccia et al 2011). Also, after 24 h, TPC-1 cells treated with 100 mM 4-IPP were lysed; the lysate was analyzed by isotope dilution mass spectrometry, as previously described (Leoni et al 2012).…”

“…Proteins secreted in the culture medium (secretome) represent activities, properties, and functional activities of tumor cells (Caccia et al 2011). We analyzed the proteins secreted by TPC-1 cells in the presence or absence of MIF inhibition to identify key mediators of the 4-IPP effects produced in TPC-1 cells.…”