Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness

Abstract

Glioblastoma multiforme (GBM) is the most malignant World Health Organization grade IV brain tumor. GBM patients have a poor prognosis because of its resistance to standard therapies, such as chemotherapy and radiation. Since stem-like cells have been associated with the treatment resistance of GBM, novel therapies targeting the cancer stem cell (CSC) population is critically required. However, GBM CSCs share molecular and functional characteristics with normal neural stem cells (NSCs). To elucidate differential therapeutic targets of GBM CSCs, we compared surface markers of GBM CSCs with adult human NSCs and found that GD2 and CD90 were specifically overexpressed in GBM CSCs. We further tested whether the GBM CSC specific markers are associated with the cancer stemness using primarily cultured patient-derived GBM cells. However, results consistently indicated that GBM cells with or without GD2 and CD90 had similar in vitro sphere formation capacity, a functional characteristics of CSCs. Therefore, GD2 and CD90, GBM specific surface markers, might not be used as specific therapeutic targets for GBM CSCs, although they could have other clinical utilities.

Multiple roles of CD90 in cancer

“…High CD90 expression was observed in high-grade gliomas [88][89][90][91]; however, conflicting results on the increased neurosphere-forming ability of CD90 + cells was reported by He et al [88] and Woo et al [91]. Nevertheless, both groups observed that CD90 + cells were distributed near the vasculature in the cancer tissue specimens which suggest their high metastatic ability and targeting CD90 might inhibit metastasis of glioma cells.…”

“…Woo et al in their recent study also found a significant overexpression of CD90 in 464T and 532T glioblastoma cells compared to the neural stem cells (cell lines 779, 682). However, they failed to find a significant difference in the in vitro tumor-forming ability between CD90 + and CD90 − populations separated from 464T glioblastoma cell line, contradicting the earlier findings and making room for further study in determining the role of CD90 in gliomas [91]. Nevertheless, Scognamiglio et al identified CD90 overexpression in atypical meningiomas (grade II) which are invasive tumors [92] and metastasize to lungs [93].…”

Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells

“…In a previous publication by Woo et al . [16], disialogangliosidase 2 (GD2) was identified as a GBM-specific antigen, in addition to a glycosphingolipid, CD90. As an initial screen, a variety of cell lines were assessed with respect to their relative expression of β4GANT 1 mRNA.…”

“…As an initial screen, a variety of cell lines were assessed with respect to their relative expression of β4GANT 1 mRNA. As a reference, we used cervical cancer HeLa cells, which have been shown to express β4GANT 1 [16]. Cell lines assessed included the colorectal HT29 and lung cancer A549 lines, expressing less or equivalent amounts of β4GANT 1 as the HeLa controls.…”

“…Poly lactic- co -glycolic acid (PLGA) is a well-established polymeric excipient (FDA approved) consisting of poly lactic acid (PLA) and poly glycolic acid (PGA). Disialogangliosidase2 (GD2) is a highly glycosylated sphingolipid which has been shown to be highly expressed in high-grade gliomas [16] in addition to several other cancer types [17]. It was also reported as a target for glioblastoma [18] but, to date, there has been no clinical development related to GBM.…”