BMP4 reverses multidrug resistance through modulation of BCL-2 and GDNF in glioblastoma

Liu, Baohui; Tian, Daofeng; Wu, Liquan; Dong, Hongyan; Wang, Junmin; Ji, Baowei; Zhu, Xiao‐Feng; Cai, Qiang; Wang, Long; Zhang, Shenqi

doi:10.1016/j.brainres.2013.02.039

Cited by 21 publications

(14 citation statements)

References 36 publications

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“…[30][31][32][33][34][35] BMP4 is one of the key regulators of UB branching, inhibiting ectopic UB outgrowth by decreasing expression of Gdnf. 34,[36][37][38] Previous work showed that Tcf21-lacZ-expressing cells are present around the stalk of the UB and express Bmp4. 27 Here, Bmp4 protein and mRNA levels were increased in Tcf21 null kidneys at E18.5 (Figure 8, A and B).…”

Section: Deletion Of Tcf21 In Stromal Progenitors Results Inmentioning

confidence: 99%

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Ide

Finer

Maezawa

et al. 2018

JASN

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Background The mammalian kidney develops through reciprocal inductive signals between the metanephric mesenchyme and ureteric bud. Transcription factor 21 (Tcf21) is highly expressed in the metanephric mesenchyme, including Six2-expressing cap mesenchyme and Foxd1-expressing stromal mesenchyme. Tcf21 knockout mice die in the perinatal period from severe renal hypodysplasia. In humans, Tcf21 mRNA levels are reduced in renal tissue from human fetuses with renal dysplasia. The molecular mechanisms underlying these renal defects are not yet known.

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Section: Deletion Of Tcf21 In Stromal Progenitors Results Inmentioning

confidence: 99%

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Ide

Finer

Maezawa

et al. 2018

JASN

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“…Liu et al [25] reported that BMP4 could reverse the multidrug resistance (MDR) phenotype of tumor cells. They generated a TMZ resistant U251 glioma cell line and observed a reduction of the BMP4 protein levels.…”

Section: Bmps As Therapeutic Targets In Astrocytic Gliomamentioning

confidence: 99%

“…Resistant cells were transfected with GFP-BMP4 and injected into nude mice brain. The treatment with TMZ was effective only in the mice overexpressing BMP4 [25]. …”

Section: Bmps As Therapeutic Targets In Astrocytic Gliomamentioning

confidence: 99%

BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

Gonzalez-Gomez

Anselmo

Mira

2014

BioMed Research International

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Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC) fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

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“…BMP4 expression is downregulated in GBM as compared to normal brain in human samples (28), suggesting that this downregulation may cause drug resistance. BMP4 reverses drug resistance, such as temozolomide, by regulating the B-cell lymphoma 2(BCL-2) and glial cell-derived neurotrophic factor (39). Thus, BMP4 may act as an important inhibitory regulator of glioma tumorigenesis to improve the therapeutic efficacy combined with conventional chemotherapy and radiation therapy (31,39,40).…”

Section: Discussionmentioning

confidence: 99%

BMP4 induces asymmetric cell division in human glioma stem-like cells

et al. 2019

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Glioblastoma (GBM) is a malignant tumor with a high recurrence rate and has very poor prognosis in humans. The median survival is still <2 years. Therefore, a new treatment strategy should be established. Recently, this cancer has been thought to be heterogeneous, consisting of cancer stem cells (CSCs) that are self-renewable, multipotent, and treatment resistant. So various strategies targeting glioma stem-like cells (GSCs) have been investigated. This study focused on strategies targeting GSCs through the induction of differentiation using bone morphogenetic protein 4 (BMP4). The expression of CD133, a cancer stem cell marker, under BMP4 treatment in GSCs was examined using flow cytometry, western blotting, and quantitative PCR. Immunofluorescent staining of GSCs was also performed to examine the type of cell division: asymmetric cell division (ACD) or symmetric cell division (SCD). We obtained the following results. The BMP4 treatment caused downregulation of CD133 expression. Moreover, it induced ACD in GSCs. While the ACD ratio was 23% without BMP4 treatment, it was 38% with BMP4 treatment (P=0.004). Furthermore, the tumor sphere assay demonstrated that BMP4 suppresses self-renewal ability. In conclusion, these findings may provide a new perspective on how BMP4 treatment reduces the tumorigenicity of GSCs.

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BMP4 reverses multidrug resistance through modulation of BCL-2 and GDNF in glioblastoma

Cited by 21 publications

References 36 publications

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

BMP4 induces asymmetric cell division in human glioma stem-like cells

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