Glioblastoma Formation from Cell Population Depleted of Prominin1-Expressing Cells

Abstract

Prominin1 (Prom1, also known as CD133 in human) has been widely used as a marker for cancer stem cells (CSCs), which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM). However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreERTM, and generated glioma-initiating cells (GICs-LD) by overexpressing both the SV40 Large T antigen and an oncogenic H-RasL61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA) form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling

“…We established a set of GIC lines by overexpressing sv40LT and hrasL61 in mouse embryonic neural stem cells (NSCs) from ecrg4 heterozygous intercrosses, as shown previously. 15 GIC(C/C) from ecrg4 C/C NSCs clearly expressed ecrg4, whereas its expression level decreased in GIC(C/¡) from ecrg4 C/¡ NSCs and was undetectable in GIC(¡/¡) from ecrg4 ¡/¡ ones (Fig. 1A).…”

“…15 The DNA fragments of mouse Ecrg4 and its deletion mutants (corresponding to amino acids 71-132 and 133-148) were amplified by PCR and subcloned into pFusehIgG1-Fc2 (InvivoGen). The primers used for amplification were as follows: For mEcrg4(71-132), sense primer 5 0 -TGGA TCCCAGCTGTGGGACCGTACGCG-3 0 and antisense primer 5 0 -TGGATCCGTGGGGACCAATGGCCGC-3 0 ; For mEcrg4 (133-148) sense primer: 5 0 -TGAATTCGAGCCGGGAAA GCTTCAGG-3 0 and antisense primer: 5 0 -TGGATCCATAGT-CATCATAGTTGACACTGG-3 0 .…”

“…Using the mouse glioma-initiating cell (GIC) models, 14,15 we addressed how Ecrg4 acts as a tumor suppressor in vivo. Unexpectedly, we found that Ecrg4 from GICs, rather than tumor-surrounding cells, was essential for its tumor-suppressor function.…”

Neuronal stem cells in the central nervous system and in human diseases

“…However, recent results suggest that CD133 expression may not be a reliable marker for the tumorigenic ability of stem cells in the brain. In the conditional knockout of the CD133 animal model, glioma can be formed from the cell population without CD133 expression (Nishide et al, 2009). In addition, both CD133-positive and CD133-negative human glioma-derived stem cell clones exhibit tumor formation ability (Chen et al, 2010).…”

CD133 Negatively Regulates TumorigenicityviaAKT Pathway in Synovial Sarcoma

“…To date, the relation of cancer stemness and proliferation activity is controversial and it also remains controversial whether CD133 is a bona fide marker for cancer stem cells [24]. While CD133 is widely used as a marker for cancer …”