Astrocytes influence medulloblastoma phenotypes and CD133 surface expression

Abstract

The medulloblastoma (MB) microenvironment is diverse, and cell-cell interactions within this milieu is of prime importance. Astrocytes, a major component of the microenvironment, have been shown to impact primary tumor cell phenotypes and metastasis. Based on proximity of MB cells and astrocytes in the brain microenvironment, we investigated whether astrocytes may influence MB cell phenotypes directly. Astrocyte conditioned media (ACM) increased Daoy MB cell invasion, adhesion, and in vivo cellular protrusion formation. ACM conditioning of MB cells also increased CD133 surface expression, a key cancer stem cell marker of MB. Additional neural stem cell markers, Nestin and Oct-4A, were also increased by ACM conditioning, as well as neurosphere formation. By knocking down CD133 using short interfering RNA (siRNA), we showed that ACM upregulated CD133 expression in MB plays an important role in invasion, adhesion and neurosphere formation. Collectively, our data suggests that astrocytes influence MB cell phenotypes by regulating CD133 expression, a key protein with defined roles in MB tumorgenicity and survival.

Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse

“…Astrocytes are important for normal brain development as well as pathological processes in the central nervous system such as neurodegenerative diseases and brain tumors. Previous studies established that TAs play a critical role in supporting the progression of MB ( Gronseth et al, 2020 ; Liu et al, 2017 ). Our lineage-tracing analyses in this study suggest that TAs in primary MB may migrate from the surrounding brain tissues.…”

Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma

“…Due to the increasing evidence between wound healing and developing tumors, recent studies are now investigating the complex functions of astrocytes in supporting medulloblastoma growth, as these specialized glial cells are involved in the functional recovery of the central nervous system (CNS) [27,30,31,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. Astrocytes are specialized and heterogeneous cells that are essentials to modulate local blood flow as well as to maintain homeostasis of extracellular fluids, ions, and transmitters [59,60].…”

“…The roles of astrocytes in the medulloblastoma microenvironment have been investigated and the studies demonstrated that astrocytes secreted CD133, a key cancer stem cell marker, involved in medulloblastoma tumorigenicity, and alter gene expression, increase invasion and adhesion ofmedulloblastoma cells [58]. Astrocytes can also have direct influence on brain tumor stem cells that are activated by several ligands, including SHH, which enrich the stem cell population.…”

Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma

“…Somatic TERT (telomerase) promoter hotspot mutations are also associated with the SHH subgroup [22,23]. Mutation of PTEN (phosphatase and tensin homolog) is found in more than 5% of human Due to increasing evidence of an association between wound healing and the development of tumors, recent studies have investigated the complex functions of astrocytes involved in the support of medulloblastoma growth, as these specialized glial cells are involved in the functional recovery of the central nervous system (CNS) [29,32,33,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Astrocytes are specialized and heterogeneous cells that are essential modulators of local blood flow as well as being involved in the maintenance of homeostasis of extracellular fluids, ions, and transmitters [61,62].…”

“…The roles of astrocytes in the medulloblastoma microenvironment have been investigated, and studies have demonstrated that astrocytes secrete CD133, a key cancer stem cell marker that is involved in medulloblastoma tumorigenicity and alters gene expression, increasing invasion and adhesion by medulloblastoma cells [60]. Astrocytes can also have a direct influence on brain tumor stem cells that are activated by several ligands, including SHH, which enriches the stem cell population [78].…”