Mapping the invasive network of glioblastoma by proteomics from laser-capture microdissected samples

Glioblastomas are brain tumors that are derived from astrocytes or oligodendrocytes. These tumors have a heterogeneous structure composed of a necrotic and vascularized center and an invasive periphery. The rapid development of glioblastoma and its ability to invade surrounding tissues makes it a complex pathology to treat, and the average survival of patients ranging from 12 to 15 months. The first and second lines of treatment, based on the Stupp protocol, consisting of the resection of the tumor mass and adjuvant temozolomide treatment and/or radiotherapy, only allow delaying recurrence for a few months. The additional use of anti-angiogenic treatment, despite its initial effects on tumor vascularization and the central tumor core, invariably leads to tumor escape. Tumor cell invasion is the central element in tumor recurrence. It is therefore important to understand the mechanisms of tumor invasion and understand the interactions between tumor cells and their microenvironment. Here, we performed proteomics analysis of glioblastoma core and invasive areas, tumor derived from a patient xenograft. Bioinformatics data analysis allowed us to identify molecules that may represent markers of tumor invasion. We established novel protein signatures such as phopholipoprotein-1 (PLP1), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) or Dynamin-1 (DNM1), and validated them in tumor samples. Finally, a functional validation was carried out in in vitro experiments. To conclude, our results report novel unexpected proteins that are involved in GBM invasion and that may constitute novel therapeutic targets.