Impact of hypoxia on the molecular content of glioblastoma-derived exosomes

Abstract

Hypoxia is a pathologic condition characterized by a tissue oxygen deficiency due to either decreased oxygen intake from outside and/or disruption of oxygen utilization in cells. This condition may arise when the oxygen demand exceeds its supply or the partial pressure of oxygen is below 10 mmHg. This situation poses a significant problem for glioblastoma (GBM) patients as it can activate angiogenesis, increase invasiveness and metastatic risk, prolong tumor survival, and suppress anti-tumor immunity, making hypoxic cells resistant to radiotherapy and chemotherapy. Low oxygen levels in tumors can cause severe cellular changes that can affect the release of extracellular vesicles (EVs), especially exosomes (EXOs), altering their proteomic profile both qualitatively and quantitatively. EXOs represent an adaptive response to hypoxic stress; therefore, they can be used to determine oxygen levels in cancer and assess its aggressiveness. They not only release signaling molecules to attract cells that promote the formation of small vessel walls but also send signals to other tumor cells that trigger their migration, which in turn plays a crucial role in the formation of metastases under hypoxia. This review investigates how the molecular profile of GBM-derived exosomes changes under hypoxic conditions, offering future possibilities for noninvasive diagnosis and monitoring of brain tumor patients.