Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells

Cheung, Sarah K.C.; Chuang, Po Kai; Huang, Han Wen; Hwang‐Verslues, Wendy W.; Cho, Candy Hsin Hua; Yang, Wen Bin; Shen, Chia‐Ning; Hsiao, Michael; Hsu, Tsui Ling; Chang, Chuan Fa; Wong, Chi Huey

doi:10.1073/pnas.1522602113

Cited by 57 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4,5,12,18,23,25,28,31,36,37,39,40,[108][109][110] Figure 1 Diagrammatic illustration of epithelial to mesenchymal transition (EMT) and interaction of cancer stem cells (CSCs) with the tumor microenvironment. EMT is influenced by multiple factors and TGFβ-induced EMT is a useful experimental model.…”

mentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

show abstract

mentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…First, having a set of antigens or markers that specifically define a cancer stem cell can facilitate isolation of relatively pure populations of these cells from heterogeneous tumors, so that the properties of the cancer stem cells can be studied. Cheung et al (1) used two assays, cell colonies and mammosphere formation, to assay the relative fraction of BCSCs from heterogeneous cultures of two different human breast cancer cell lines. The group defined a repertoire of antigens that yielded a significantly enriched population of BCSCs from both human cell lines.…”

Section: Glycoantigens On Cancer Stem Cellsmentioning

confidence: 99%

“…Given the ease of flow cytometry and the heterogeneity of tumor cell populations, rigorous structural analysis of glycolipid epitopes is not typically part of a study examining the biological properties of cancer stem cells. However, the work by Wong and coworkers (1) demonstrates that detection of an epitope by flow cytometry (i.e., the relative fluorescence of the number of tagged antibodies bound to the cell surface) may not directly reflect the abundance of the structures being interrogated. This lack of correlation may reflect the accessibility of the epitope to the antibody on the cell surface, the distribution of the epitopes on the cell surface, or the cross-reactivity of the antibody with related epitopes.…”

Section: Beyond Flow Cytometrymentioning

confidence: 99%

“…An advantage of mass spectrometry is that the structures that are identified are clearly defined; however, because isolation of the pool of cells to be analyzed by mass spectrometry may require antibody-mediated isolation, there will continue to be a trade-off between the utility of rapid screening techniques such as flow cytometry and the more definitive characterization offered by mass spectrometry. Cheung et al (1) stress that the development of better reagents to detect these glycolipid antigens will benefit the field.…”

Section: Beyond Flow Cytometrymentioning

confidence: 99%

“…It is now clear that tumors are indeed composed of very different, genetically distinct subpopulations of cancer cells and that a tiny fraction of those cells, the cancer stem cells, are endowed with the ability to self-renew and to persist and thus can establish new tumors. In PNAS, Cheung et al (1) identify a specific glycolipid antigen, stage-specific embryonic antigen-3 (SSEA-3), that is preferentially expressed on a small fraction of cultured breast cancer cells that fulfill the definition of cancer stem cells. Importantly, this paper also identifies a single gene product, the β-1,3-galactosyltransferase 5 (β3GalT5) enzyme, that creates a critical domain of this glycolipid antigen (see figure S3 in ref.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Sweet beginning for cancer stem cells

Baum

2016

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

View full text Add to dashboard Cite

Chemoenzymatic Synthesis of DSGb5 and Sialylated Globo‐series Glycans

Huang

Chiang

et al. 2019

Angewandte Chemie

View full text Add to dashboard Cite

Sialic-acid-binding,i mmunoglobulin-type lectin-7 (Siglec-7) is present on the surface of natural killer cells.Siglec-7s hows preference for disialylated glycans,i ncluding a(2,8)a(2,3)-disialic acids or internally branched a(2,6)-NeuAc,such as disialosylglobopentaose (DSGb5). Herein, DSGb5 was synthesized by ao ne-pot multiple enzyme method from Gb5 by a2,3-sialylation (with PmST1) followed by a2,6-sialylation (with Psp2,6ST) in 23 %o verall yield. DSGb5 was also chemoenzymatically synthesized. The protection of the nonreducing-end galactose of Gb5 as 3,4-O-acetonide,3 ,4-Obenzylidene,a nd 4,6-O-benzylidene derivatives provided DSGb5 in overall yields of 26 %, 12 %, and 19 %, respectively. Gb3, Gb4, and Gb5 were enzymatically sialylated to afford ar ange of globo-glycans.S urprisingly,D SGb5 shows al ow affinity for Siglec-7 in ag lycan microarray binding affinity assay. Among the synthesized globo-series glycans, a6a3DSGb4 shows the highest binding affinity for Siglec-7.Globosides,stage-specific embryonic antigen-4 (SSEA4, MSGb5, or a3SGb5 in Scheme 1) and disialosylglobopentaosylceramide (DSGb5-Cer), are expressed in relatively large amounts on the surface of cancer cells,including renal cancer cells (RCC), and they are associated with cancer proliferation and metastasis. [1] Therefore,g lobosides have been used for cancer detection [2] and vaccine development. [3] Thes tructure of DSGb5-Cer was determined in 1994, [4] and it is an interesting target since its total synthesis has not been reported. Theh igh affinity of DSGb5-Cer for Siglec-7 (sialic acid-binding immunoglobulin-type lectin-7) was reported in 2011. [5] Siglec-7 is al ectin present on the surface of natural killer (NK) cells as an inhibitory receptor of NK cell cytotoxicity. [6] Later, glycans with a2,8-a2,3-disialic acid or internally branched a2,6-NeuAc were shown to be potent ligands for Siglec-7 in competitive binding assays. [7] In nature, NK cell cytotoxicity is modulated by cis interactions between Siglec-7 and endogenous sialoconjugates on the cell surface. [6] By treating NK cells with sialidase to remove NeuAc and disrupt the cis interactions,t he unmasked Siglec-7 can interact with DSGb5-Cer on the surface of the human renal cancer cell line ACHN,decreasing the cytotoxicity of the NK cells and promoting the metastasis and invasion of RCC. [8] Obtaining as ufficient amount of pure DSGb5 is key to elucidating its mechanism of action and to further develop cancer immunotherapies.C larifying the binding activities of sialylated globo-series glycans and the effect of the NeuAc position on their interactions with Siglec-7 is also of great interest.Thee nzymatic and chemoenzymatic syntheses of globoseries glycans,such as Gb5, SSEA-4, and Globo H, have been reported by several research groups, [9][10][11] but no method has been reported for the synthesis of DSGb5. DSGb5 has aunique glycan structure with two NeuAcs as a2,3-and a2,6linkages on the nonreducing-end galactose (Gal) and Nacetylgalactosamine (GalNAc), respectively,o fG b5 (Figure 1)....

show abstract

Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells

Cited by 57 publications

References 28 publications

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Sweet beginning for cancer stem cells

Chemoenzymatic Synthesis of DSGb5 and Sialylated Globo‐series Glycans

Contact Info

Product

Resources

About