Glycomic profiling of invasive and non-invasive breast cancer cells

Goetz, John A.; Mechref, Yehia; Kang, Pilsoo; Jeng, Meei-Huey; Novotný, Miloš V.

doi:10.1007/s10719-008-9170-4

Cited by 86 publications

(78 citation statements)

References 29 publications

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“…Very similar pattern and significant decrease in sialylation and fucosylation in breast cancer cell lines was recently reported by Goetz at al. 50 In our study, the largest glycans was observed at m/z 3997.4 and its composition corresponded to a tetra-antennary core fucosylated structure with bisecting moiety and NeuAc residues on each antenna (Figure 2a, Table 1). Due to low intensity, CID spectra of sialylated glycans were noisier than others discussed above, however the signal was sufficient for structural investigation.…”

Section: Maldi-ms Analysis Of N-glycans From Mcf-7 and Cemsupporting

confidence: 49%

N-Glycomic Changes in Human Breast Carcinoma MCF-7 and T-Lymphoblastoid Cells After Treatment with Herceptin and Herceptin/Lipoplex

et al. 2010

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The humanized monoclonal antibody IgG1 in combination with chemotherapy has been demonstrated to enhance survival benefit in cancer treatment. Despite positive outcomes, some cancer cells develop multidrug resistance. Numerous mechanisms in cancers can be involved in the process of treatment therapy and most of them are not still well understood. To address how the carbohydrate moieties of cells are affected during treatment, the glycan profiles from the two most common cancer cell lines s human breast MCF-7 carcinoma and T-lymphoblastoid CEM cells s were studied here and compared with profiles after treatment with Herceptin alone or in combination with Lipofectamine mixed with plasmid DNA to form Lipoplex. N-Glycans were released from total cells by digestion with PNGaseF and analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). In summary, both original cell lines showed a dominant occurrence of high-mannose glycans. After treatment, these structures were suppressed and biantennary core-fucosylated glycans originating from IgG1 were the major carbohydrate products identified in cells. The high incidence of additional fucosylated or nonfucosylated galactosylated oligosaccharides, which were not detected in original cells or Herceptin, varied with conditions and time of exposure of cells to the antibody. The results presented in this study provide strong evidence for a role of glycosylation during antibody treatment.

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Section: Maldi-ms Analysis Of N-glycans From Mcf-7 and Cemsupporting

confidence: 49%

N-Glycomic Changes in Human Breast Carcinoma MCF-7 and T-Lymphoblastoid Cells After Treatment with Herceptin and Herceptin/Lipoplex

et al. 2010

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“…A similar study involving cytosolic glycoproteins from breast cancer cell lines also showed that high mannose N-glycans were significantly elevated in invasive and noninvasive breast cancer cells as compared with the normal breast epithelial cells (83). Although it remains unclear whether high mannose glycans are a common feature of most cultured cell lines, the presence of high mannose structures reported here correlates with the study by Jacob et al (2012) who showed that naturally occurring anti-glycan antibodies such as anti-Man, present in ovarian cancer patients' plasma exhibited specific binding of high mannose structures using a printed glycan-array technology (23).…”

Section: Gene Expression Of Specific Glycosyltransferases In Ovarian mentioning

confidence: 68%

Specific Glycosylation of Membrane Proteins in Epithelial Ovarian Cancer Cell Lines: Glycan Structures Reflect Gene Expression and DNA Methylation Status

Anugraham

Jacob

Nixdorf

et al. 2014

Molecular & Cellular Proteomics

127

152

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Epithelial ovarian cancer is the fifth most common cause of cancer in women worldwide bearing the highest mortality rate among all gynecological cancers. Cell membrane glycans mediate various cellular processes such as cell signaling and become altered during carcinogenesis. The extent to which glycosylation changes are influenced by aberrant regulation of gene expression is nearly unknown for ovarian cancer and remains crucial in understanding the development and progression of this disease. To address this effect, we analyzed the membrane glycosylation of non-cancerous ovarian surface epithelial (HOSE 6.3 and HOSE 17.1) and serous ovarian cancer cell lines (SKOV 3, IGROV1, A2780, and OVCAR 3), the most common histotype among epithelial ovarian cancers. Nglycans were released from membrane glycoproteins by PNGase F and analyzed using nano-liquid chromatography on porous graphitized carbon and negative-ion electrospray ionization mass spectrometry (ESI-MS). Glycan structures were characterized based on their molecular masses and tandem MS fragmentation patterns. We identified characteristic glycan features that were unique to the ovarian cancer membrane proteins, namely the "bisecting N-acetyl-glucosamine" type N-glycans, increased levels of ␣ 2-6 sialylated N-glycans and "N,N-diacetyllactosamine" type N-glycans. These N-glycan changes were verified by examining gene transcript levels of the enzymes specific for their synthesis (MGAT3, ST6GAL1, and B4GALNT3) using qRT-PCR. We further evaluated the potential epigenetic influence on MGAT3 expression by treating the cell lines with 5-azacytidine, a DNA methylation inhibitor. For the first time, we provide evidence that MGAT3 expression may be epigenetically regulated by DNA hypomethylation, leading to the synthesis of the unique "bisecting GlcNAc" type N-glycans on the membrane proteins of ovarian cancer cells. Linking the observation of specific N-glycan substructures and their complex association with epigenetic programming of their associated synthetic enzymes in ovarian cancer could potentially be used for the development of novel anti-glycan drug targets and clinical diagnostic tools. Molecular & Cellular

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“…For example, Man 5 -Man 7 glycans were present in mice implanted with head and neck tumor but not in healthy mice (29). In a different study, Man 5 -Man 8 glycans were statistically elevated in the soluble cytosolic glycoproteins isolated from invasive and noninvasive breast cancer cells compared with those isolated from normal epithelial cells (32). Another report (33) shows high mannose oligosaccharides to be more prevalent in the cell surface of tumor cells compared with normal cells.…”

Section: Distinct Differences In N-linked Glycan Intensities Between mentioning

confidence: 95%

High-Mannose Glycans are Elevated during Breast Cancer Progression

Leoz

Young²,

et al. 2011

Molecular & Cellular Proteomics

274

233

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Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes in glycosylation. We have previously used the said mouse model to look at O-linked glycosylation changes with breast cancer. In this glycan biomarker discovery study, we examined N-linked glycan variations during breast cancer progression of the mouse model but this time doubling the number of mice and blood draw points. N-glycans from total mouse serum glycoproteins were profiled using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry at the onset, progression, and removal of mammary tumors. Breast cancer is the leading cause of cancer death and the most frequently diagnosed cancer among women worldwide (1). In the United States alone, ϳ40,000 deaths and 210,000 new cases were expected in 2010 (2). Incidence rates continue to rise especially in many developing and westernized countries. Unfortunately, early stages of breast cancer show no noticeable symptoms. Early diagnosis is critical because the chance of survival is greater in early stage (Stage I and II) breast cancer. It is estimated that 98% of U. S. women will survive longer than 5 years if the cancer is detected early. At late stages (Stages III and IV), however, only 28% will survive longer than 5 years (1).Currently, carbohydrate antigen 15-3 (CA 15-3) is the most common clinical serum marker for breast cancer. This marker uses immunoassay to detect MUC-1, a mucin glycoprotein overexpressed with breast cancer. Other markers for breast cancer include carcinoembryonic antigen, an anchored glycoprotein involved in cell adhesion, and CA 27.29, another MUC-1-derived glycoprotein marker. A common feature of these three markers is that all are proteins containing glycoforms.However, the current markers described above are not recommended by the American Society of Clinical Oncology as markers for screening, diagnostic, or staging tests for breast cancer (3). During the early stages of breast cancer, the sensitivity (i.e. patients correctly identified) of these markers is less than 25% (3-7). Moreover, the specificity (i.e. people without cancer correctly identified) is also problematic: up to 20%-30% of women without breast cancer, i.e. healthy individuals, women with benign breast lesions, people with benign diseases such as liver disease, and people with other types of advanced adenocarcinoma, have elevated levels of the said markers (3-7). Thus, an elevated marker level is not specific to breast cancer and may lead to false positive diagnoses for the healthy individual.Aberrant glycosylation is observed in the progression of many types of diseases, including different cancers (8, 9). Glycosylation, one of the most common forms of post-translational modification, is highly sensitive to ...

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Glycomic profiling of invasive and non-invasive breast cancer cells

Cited by 86 publications

References 29 publications

N-Glycomic Changes in Human Breast Carcinoma MCF-7 and T-Lymphoblastoid Cells After Treatment with Herceptin and Herceptin/Lipoplex

N-Glycomic Changes in Human Breast Carcinoma MCF-7 and T-Lymphoblastoid Cells After Treatment with Herceptin and Herceptin/Lipoplex

Specific Glycosylation of Membrane Proteins in Epithelial Ovarian Cancer Cell Lines: Glycan Structures Reflect Gene Expression and DNA Methylation Status

High-Mannose Glycans are Elevated during Breast Cancer Progression

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