Ganglioside GD2 Identifies Breast Cancer Stem Cells and Promotes Tumorigenesis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2012 May 16

PMID 22585577

Citations 161

Authors

Venkata Lokesh Battula

Yuexi Shi

Kurt W Evans

Rui-Yu Wang

Erika L Spaeth

Rodrigo O Jacamo

Rudy Guerra

Aysegul A Sahin

Frank C Marini

Gabriel Hortobagyi

Sendurai A Mani

Michael Andreeff

Affiliations

Soon will be listed here.

Abstract

Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have increased resistance to conventional therapies and are capable of establishing metastasis. However, only a few biomarkers of CSCs have been identified. Here, we report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of cells in human breast cancer cell lines and patient samples that are capable of forming mammospheres and initiating tumors with as few as 10 GD2+ cells. In addition, the majority of GD2+ cells are also CD44hiCD24lo, the previously established CSC-associated cell surface phenotype. Gene expression analysis revealed that GD3 synthase (GD3S) is highly expressed in GD2+ as well as in CD44hiCD24lo cells and that interference with GD3S expression, either by shRNA or using a pharmacological inhibitor, reduced the CSC population and CSC-associated properties. GD3S knockdown completely abrogated tumor formation in vivo. Also, induction of epithelial-mesenchymal transition (EMT) in transformed human mammary epithelial cells (HMLER cells) dramatically increased GD2 as well as GD3S expression in these cells, suggesting a role of EMT in the origin of GD2+ breast CSCs. In summary, we identified GD2 as a new CSC-specific cell surface marker and GD3S as a potential therapeutic target for CSCs, with the possibility of improving survival and cure rates in patients with breast cancer.

Citing Articles

Correlation of GD2 Biosynthesis Enzymes With Cancer Stem Cell Markers in Human Breast Cancer.

ONeill N, Rizk M, Li A, Martin T, Jiang W, Mokbel K Cancer Genomics Proteomics. 2025; 22(2):231-246.

PMID: 39993803 PMC: 11880921. DOI: 10.21873/cgp.20498.

Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma.

Li C, Sharma S, Heczey A, Woods M, Steffin D, Louis C Nat Med. 2025; .

PMID: 39962287 DOI: 10.1038/s41591-025-03513-0.

True cancer stem cells exhibit relative degrees of dormancy and genomic stability.

Barsky S, Mcphail K, Wang J, Dillard J, Beard C, Ye Y Neoplasia. 2025; 60:101127.

PMID: 39847828 PMC: 11795081. DOI: 10.1016/j.neo.2025.101127.

Current status and innovative developments of CAR-T-cell therapy for the treatment of breast cancer.

Marei H, Bedair K, Hasan A, Al-Mansoori L, Caratelli S, Sconocchia G Cancer Cell Int. 2025; 25(1):3.

PMID: 39755633 PMC: 11700463. DOI: 10.1186/s12935-024-03615-8.

Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma.

Mannini A, Pastore M, Giachi A, Correnti M, Spinola Lasso E, Lottini T Liver Int. 2024; 45(1):e16208.

PMID: 39726234 PMC: 11684508. DOI: 10.1111/liv.16208.

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