Comparative Proteomic Analysis of Tumor Mesenchymal-Like Stem Cells Derived from High Grade versus Low Grade Gliomas

Gliomas are the most common primary brain tumors, and have been ranked as the fourth leading cause of cancer death. Tumor mesenchymal-like stem cells (tMSCs) contribute to the aggressive behavior of glial tumors by providing a favorable microenvironment for the malignant cells. The aim of our study was to identify differential proteome of tMSCs derived from low vs. high grade glioma tumors.

Patients with newly diagnosed low and high grade gliomas were included in this case control study. tMSCs were isolated from tumors using enzymatic digestion validated by flow cytometer analysis after sub-culturing. Differential proteomic analysis of tMSCs derived from low and high grade tumors was performed by two-dimensional gel electrophoresis and mass spectrometry. Protein spots with more than two fold differences and P values below 0.05 were considered as differentially expressed ones.

In tMSCs isolated from low and high grade gliomas, different isoforms of mesenchymal-related proteins vimentin and transgelin were differentially expressed. Overexpressed proteins in tMSCs isolated from low grade gliomas were mitochondrial manganese-containing superoxide dismutase (Mn-SOD), 40S ribosomal protein SA, and GTP-binding nuclear protein, while in tMSCs isolated from high grade gliomas, cathepsin B, endoplasmin, ezrin, peroxiredoxin1, and pyruvate kinase (PK) were found to be significantly overexpressed.

For the first time, we analyzed the differential proteomic profiles of tMSCs isolated from glioma tumors with different grades. It was found that molecules related to mesenchymal cells (vimentin and transglin), in addition to those related to tumor aggressiveness with potential secretory behavior (e.g. cathepsin B) were among differentially expressed proteins.