Tumor Microenvironment in Glioma Invasion

Abstract

A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain.

Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma

“…Studies on the role of tumor microenvironment in glioma invasion have been expanding in recent years. Tumor cells degrade surrounding ECM by secreting protease, resulting in tumor invasion ( Tamai et al, 2022 ). MFAP2 is a key ECM glycoprotein and protein component of ECM microfibrils.…”

The complex interactions between the cellular and non-cellular components of the brain tumor microenvironmental landscape and their therapeutic implications

“…On the other hand, the brain parenchyma is rich in glycosaminoglycans (hyaluronic acid), proteoglycans and other linking proteins ( 6 , 7 ). Compared to the healthy brain, the ECM is altered in GBM tumors and plays a crucial role in tumor invasion and migration ( 3 , 4 ). Higher concentrations of collagen, fibronectin, laminin, hyaluronic acid, tenascin C, and vitronectin are present in the ECM of GBM and have been shown to have important roles in the onset and glioma progression ( Figure 2 ) ( 4 , 5 ).…”

“…Aside from malignant cells, tumors are comprised of vascular cells and immune cells (macrophages, microglia, and T, B, and NK cells) -which in gliomas can amount to 50% of the total number of cells in the tumor- in addition to the extracellular matrix ( 2 ). The ECM is modified in GBM tumors compared to the normal brain, playing a critical role in tumor migration and invasion ( 3 , 4 ). In GBM, the ECM consists of higher levels of collagen, fibronectin, laminin, hyaluronic acid, tenascin-C and vitronectin ( 4 , 5 ) and the exact composition of any individual tumor varies with the stage of tumor growth as the extracellular matrix becomes more remodeled ( 6 , 7 ).…”

“…The ECM is modified in GBM tumors compared to the normal brain, playing a critical role in tumor migration and invasion ( 3 , 4 ). In GBM, the ECM consists of higher levels of collagen, fibronectin, laminin, hyaluronic acid, tenascin-C and vitronectin ( 4 , 5 ) and the exact composition of any individual tumor varies with the stage of tumor growth as the extracellular matrix becomes more remodeled ( 6 , 7 ).…”

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

“…Gliomas still have low cure rates, high recurrence rates, and poor prognosis [2][3][4]. The immunosuppressive tumor microenvironment that develops during glioma and infiltrative growth of glioma are the main reasons for the poor outcome of glioma treatment [5][6][7][8].…”