The Role of Inflammation in Brain Cancer

Abstract

Malignant brain tumors are among the most lethal of human tumors, with limited treatment options currently available. A complex array of recurrent genetic and epigenetic changes has been observed in gliomas that collectively result in derangements of common cell signaling pathways controlling cell survival, proliferation, and invasion. One important determinant of gene expression is DNA methylation status, and emerging studies have revealed the importance of a recently identified demethylation pathway involving 5-hydroxymethylcytosine (5hmC). Diminished levels of the modified base 5hmC is a uniform finding in glioma cell lines and patient samples, suggesting a common defect in epigenetic reprogramming. Within the tumor microenvironment, infiltrating immune cells increase oxidative DNA damage, likely promoting both genetic and epigenetic changes that occur during glioma evolution. In this environment, glioma cells are selected that utilize multiple metabolic changes, including changes in the metabolism of the amino acids glutamate, tryptophan, and arginine. Whereas altered metabolism can promote the destruction of normal tissues, glioma cells exploit these changes to promote tumor cell survival and to suppress adaptive immune responses. Further understanding of these metabolic changes could reveal new strategies that would selectively disadvantage tumor cells and redirect host antitumor responses toward eradication of these lethal tumors.

Characterization of Inflammatory Changes Associated with Canine Oligodendroglioma

“…microglia in the CNS, Kupffer cells in the liver) as well as regional necrosis and hypoxia that draws in inflammatory cells (Sowers et al, 2014). Indeed, differences in the immune cell infiltrate may also correlate with the breed of the dog (Villaescusa et al, 2012).…”

“…The inflammatory microenvironment associated with neoplasia has an important role in the stages of tumour development including initiation, progression and invasion (Sowers et al, 2014). Chronic mediators of inflammation, especially lymphocytes and macrophages, are often found widely throughout a variety of tumours; however, their significance is either unknown or varies depending on the specific tumour.…”

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

“…The microenvironment of glioblastoma tumors is characterized by the infiltration of hyperactivated immune cells, which aggravate disease progression. Thus, it can be hypothesized that inhibition of lipid metabolism can also reduce inflammation at tumor sites [88][89][90]. However, the potential side effects of pyrrolidine-2 deter its use in vivo.…”

Genome-wide pathway analysis in glioma

“…LPS induces nitric oxide (NO) in rat glioma C6, suggesting NO derived from inflammation may contribute to the progression of carcinogenesis [16]. Inflammatory responses may play a key role in the pathogenesis of brain tumor [17]. The fifth mechanism was that rs4644 and rs4652 regulate LGALS3, affecting immunoglobulin binding.…”

“…The sixth pathway was acute inflammatory response. It is well known that inflammation plays important roles in the pathogenesis of brain tumor [17]. The seventh pathway was macrophage activation, which leads to change in the morphology and behavior of a macrophage resulting from exposure to a cytokine, chemokine, or cellular ligand, and plays a key role in the immune and inflammatory responses.…”