Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis

Battula, Venkata Lokesh; Shi, Yuexi; Evans, Kurt W.; Wang, Rui Yu; Spaeth, Erika L.; Jácamo, Rodrigo; Guerra, Rudy; Şahin, Ayşegül; Marini, Frank C.; Hortobágyi, Gabriel N.; Mani, Sendurai A.; Andreeff, Michael

doi:10.1172/jci59735

Cited by 236 publications

(271 citation statements)

References 44 publications

(47 reference statements)

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“…GD2-CAR T cells could induce complete tumor responses in patients with active neuroblastomas (57). In addition, GD2 was characterized as a maker of cancer stem cells in breast cancer, indicating that GD2-targeted therapy might eliminate cancer stem cells (58). Our findings that GD3 and/or GD2 are specifically expressed in glioma tissues in adult brain and play roles in the modulation of PDGFR␣/Yes/paxillin signaling, leading to the increased invasion, provide approaches for the development of novel therapeutics targeting there gangliosides for glioma patient.…”

Section: Discussionmentioning

confidence: 99%

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

Ohkawa

Momota

Kato

et al. 2015

Journal of Biological Chemistry

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Background: Roles of GD3 in gliomas are not well understood. Results: PDGF receptor ␣ was identified as a GD3-associated molecule by enzyme-mediated activation of radical sources and mass spectrometry, and its association with GD3 and Yes leads to increased invasiveness. Conclusion: GD3 enhances invasiveness by forming a molecular complex. Significance: GD3/PDGF receptor ␣⅐Yes complex is a potential target for glioma therapy.

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Section: Discussionmentioning

confidence: 99%

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

Ohkawa

Momota

Kato

et al. 2015

Journal of Biological Chemistry

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“…GD3S has been reported to be a potential therapeutic target for inhibiting breast cancer initiation (34), but the expression status of GD3S in GBM tissues was unclear. To investigate whether GD3S was overexpressed in clinical GBM specimens, we analyzed the expression of GD3S in grade I-IV astrocytomas and in normal brain tissues by screening human tissue arrays using immunohistochemistry.…”

Section: Resultsmentioning

confidence: 99%

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

Yeh

Wang

Lou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133 − cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20-30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complementdependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM.GBM | ST8SIA1 | gangliosides | glycosphingolipids | cancer stem cells

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“…However, GD2 is highly expressed in human tumors of neuroectodermal origin, including neuroblastomas, melanomas, gliomas, small cell lung carcinomas (SCLC), Ewing sarcomas as well as in osteosarcomas and some soft-tissue sarcomas [191]. Recently, it has been shown that GD2 is expressed on highly tumorigenic CSCs isolated and enriched from human breast cancer cell lines or breast cancer patient samples [193], thus identifying GD2 as a putative cell surface target for mAb-mediated eradication of breast CSCs. Because of the relatively selective expression of GD2 on the cell surface of neuroectodermal tumors and breast CSCs, GD2 is an attractive and promising target for tumor-specific antibody therapy.…”

Section: Anti-gd2mentioning

confidence: 99%

“…In view of the recent discovery that GD2 is expressed on human breast CSCs and promotes tumorigenesis in human breast cancer xonograft mice [193], mAbs and antibody constructs targeting GD2 may represent powerful therapeutic tools for the eradication of breast CSCs and the treatment of human breast cancer and other GD2-expressing tumors. …”

Section: Anti-gd2mentioning

confidence: 99%

Targeting Human Cancer Stem Cells with Monoclonal Antibodies

Naujokat¹

2012

J Clin Cell Immunol

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Cancer stem cells (CSCs) constitute a distinct subpopulation of tumor cells that exhibit self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of cancer cells that comprise the tumor. CSCs possess various intrinsic mechanisms of resistance to conventional chemotherapeutics, novel tumor-targeted drugs and radiation therapy, permitting them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Different cell surface and transmembrane proteins expressed by CSCs, including CD44, CD47, EpCAM (CD326), CD123, CD133, GD2, Lgr5, insulin-like growth factor receptor I (IGF-IR), and members of the Notch and Wnt signaling pathways, have been identified and mainly used for the characterization of CSCs in experimental settings. Recently, monoclonal antibodies and antibody constructs such as Triomabs and BiTEs raised against these CSC proteins have shown efficacy against CSCs in human xenograft mice, and some of them have been demonstrated to induce tumor regression in clinical trials.Since current cancer therapies fail to eliminate CSCs, ultimately leading to cancer recurrence and progression, selective targeting of CSCs with mAbs and antibody constructs reviewed herein may represent a novel and promising therapeutic strategy to eradicate cancer.

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Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis

Cited by 236 publications

References 44 publications

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

Targeting Human Cancer Stem Cells with Monoclonal Antibodies

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