Sox2 Expression in Brain Tumors: A Reflection of the Neuroglial Differentiation Pathway

Abstract

Sox2 is a key transcription factor that maintains the proliferation of neuroglial stem cells and inhibits neuronal fate commitment. Moreover, it was recently found that brain tumors contain stem cells that resemble normal neuroglial stem cells in many respects. This study was undertaken to describe Sox2 expression in various brain tumors, and to determine whether Sox2 expression is a universal feature of brain tumors, or whether its expression is limited to a specific lineage of brain tumors. Sox2 immunohistochemistry was performed on 194 brain tumor tissues of various kinds. Fetal and adult normal brain tissues obtained by autopsy and brain tissues of epilepsy patients with cortical dysplasia were used as controls. Semiquantitative reverse transcription polymerase chain reaction was used to confirm the immunohistochemical results. Double immunofluorescence was performed to characterize the lineage of Sox2-positive cells. Sox2 was found to be expressed in various glial tumors, including those with astroglial, oligodendroglial, and ependymal lineages, and in the glial components of mixed neuroglial tumors, regardless of pathologic grade. In brain tumors of embryonal origin, supratentorial primitive neuroectodermal tumors showed robust Sox2 expression, whereas medulloblastomas and pineoblastomas did not. The majority of Sox2-positive tumor cells coexpressed glial fibrillary acidic protein, and most Sox2-negative cells in medulloblastomas and pineoblastomas showed neuronal differentiation. This study suggest that Sox2 may be a tumor marker of glial lineages rather than a universal brain tumor stem cell marker, because its expression pattern was found to correspond to differentiation pathways. On the other hand, the aberrant coexpressions of Sox2 and of a neuronal marker were widely observed in glioblastomas, which reflects a disorganized differentiation pattern that characterizes highly malignant tumors.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Many markers potentially specific for GSCs have been proposed such as A2B5 cell surface ganglioside epitope (A2B5) [26,27], aldehyde dehydrogenase (ALDH) [28], BMI1 polycomb ring finger oncogene (BMI1) [29,30], fucosyltransferase 4 (FUT4) (CD15) [31], Thy-1 cell surface antigen (Thy-1) (CD90) [32], prominin-1 (PROM1) (CD133) [5,6], chemokine (C-X-C motif) receptor 4 (CXCR4) [33], inhibitor of DNA binding 1 (ID1) [34], integrin α6 (ITGA6) [35], L1 cell adhesion molecule (L1CAM) [36], maternal embryonic leucine zipper kinase (MELK) [37], musashi-1 (msi1) [38], nestin (NES) [38][39][40], octamer-binding transcription factor 4 (OCT4) [41], OLIG2 [42] and SOX2 [38,[43][44][45]. Among these, much attention has been given to CD133, which is currently used to identify and isolate GSCs [40,43,[46][47][48][49][50].…”

SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity

“…27 Chen et al 28 These observations indicate that SOX2 has a role in tumorigenicity of both gliomas and lung adenocarcinomas in vivo; however, its exact molecular mechanisms are still elusive.…”

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

“…Several kinds of tumors, including lung, stomach, breast cancers and gliomas, showed SOX2 overexpression. [41][42][43][44] Recently, two studies demonstrated that SOX2 expression was correlated with lymph node metastasis, distant spread, and poor prognosis in colorectal carcinoma patients. 31,45 The NOTCH signaling pathway is an evolutionarily conserved intercellular signal transfer system regulating cell differentiation, proliferation, and apoptosis.…”