Bone Morphogenetic Protein 4 Inhibits Cell Proliferation and Induces Apoptosis in Glioma Stem Cells

Zhou, Zhimin; Sun, Lihua; Wang, Yingyi; Wu, Zhifeng; Geng, Jiong; Miu, Weifeng; Pu, Yang; You, Yongping; Yang, Zhengxiang; Liu, Ning

doi:10.1089/cbr.2010.0857

Cited by 31 publications

(24 citation statements)

References 24 publications

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“…Zhou et al [24] observed that BMP4 may act as a key inhibitory regulator of cancer initiation and therefore may be used in combined stem cell-based therapy as a noncytotoxic therapeutic agent. The CD133+ GIC fraction used in this study was isolated from the human glioma cell line U87 by using vincristine and was exposed to the BMP4 protein.…”

Section: Bmp Effects On Glioma Initiating Cellsmentioning

confidence: 99%

“…As we explained above, BMPs have been shown to promote GIC differentiation and to reduce GBM proliferation in vitro and in vivo [23, 24, 29–31, 38], so they are becoming promising therapeutic tools that could be used in combination with other conventional treatments (Figure 1). This has been recently explored by several groups.…”

Section: Bmps As Therapeutic Targets In Astrocytic Gliomamentioning

confidence: 99%

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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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Section: Bmp Effects On Glioma Initiating Cellsmentioning

confidence: 99%

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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“…[1][2][3][4][5][6] Regarding the effect of BMP4 on tumors, BMP4 was shown to induce differentiation in CSCs and suppress tumor growth in glioblastoma and colon cancer. 4,5 Zhou et al 7 reported that BMP4 inhibited proliferation and induced apoptosis in glioma stem cells. Because BMP4 is originally expressed in the neural crest during the development of the embryo, 8 it may play a particular role in the regulation of neural cancer cells.…”

Section: Introductionmentioning

confidence: 99%

BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors

et al. 2013

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Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy.

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“…BMPs have been either inhibitory or stimulatory in central nervous system-associated tissues. BMP4 inhibits glioma stem cell proliferation (Zhou et al, 2011;Kallionemi, 2012) but stimulates pituitary adenoma cells and inhibits primitive neuroectodermal cell apoptosis (Intoska, et al, 1999;Paez-Pereda et al, 2003,). BMP4 stimulation of other select mesodermal and epithelial cells has also been described (Yang et al, 2007, Montesano et al, 2008.…”

Section: D Bmp Regulation Of Proliferation In Neoplasia Including Mmentioning

confidence: 99%

Transforming Growth Factor-beta Superfamily in Meningiomas: Targets for Novel Therapy in eningiomas

Johnson

2015

IJN

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Meningiomas are central nervous system tumors with a high recurrence rate. In the absence of effective chemotherapies, inoperable, recurrent and metastatic tumors remain a therapeutic challenge. Members of the TGF- super-family play an integral role in the development, progression and metastases of many malignancies yet may be underappreciated participants in the biology of meningiomas. This paper reviews the common abnormalities in TGF- or BMP signaling in neoplasias with a focus on meningiomas. Sites of potential targeting for new chemotherapies are also noted.

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Bone Morphogenetic Protein 4 Inhibits Cell Proliferation and Induces Apoptosis in Glioma Stem Cells

Cited by 31 publications

References 24 publications

BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors

Transforming Growth Factor-beta Superfamily in Meningiomas: Targets for Novel Therapy in eningiomas

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