Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types

Abstract

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.

Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model

“…The GBM microenvironment is a complex, dynamic, and interactive system. GBM cells and various components of the TME influence each other directly through cell-cell contact or indirectly through the release of soluble factors, such as cytokines, chemokines, growth factors, and extracellular matrix (ECM) remodeling enzymes, as well as via extracellular vesicles (EVs) [21][22][23][24][25][26]. In addition to these communication mechanisms, GBM cells use nanotubes, gap junctions, free DNA, horizontal DNA transfer, and circulating tumor cells to interact with other tumor and non-tumor cells.…”

“…In addition to these communication mechanisms, GBM cells use nanotubes, gap junctions, free DNA, horizontal DNA transfer, and circulating tumor cells to interact with other tumor and non-tumor cells. Overall, this complex communication network between GBM cells and TME components characterized by the release of altered metabolic products and chemical factors, such as pH and oxygen levels, promotes the proliferation, invasion, migration, and survival of GBM tumor cells [21,[27][28][29]. Although GBM does not spread beyond nervous system structures, it represents a highly invasive tumor capable of rapidly spreading to surrounding tissues through the perivascular space of nearby blood vessels, through the space between neurons and neuroglia, or/and through the white matter fiber bundles.…”