Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Diluka Peiris; Alexander F. Spector; Hannah Lomax-Browne; Tayebeh Azimi; Bala Ramesh; Marilena Loizidou; Hazel Welch; Miriam V. Dwek

doi:10.1038/srep43006

journal article Open Access Feb 22, 2017

Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Diluka Peiris Alexander F. Spector Hannah Lomax-Browne Tayebeh Azimi Bala Ramesh Marilena Loizidou Hazel Welch Miriam V. Dwek

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep43006

Abstract

AbstractAlterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 μM DXR P < 0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P < 0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer.

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Published: Feb 22, 2017
Vol/Issue: 7(1)
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Cite This Article

Diluka Peiris, Alexander F. Spector, Hannah Lomax-Browne, et al. (2017). Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors. Scientific Reports, 7(1). https://doi.org/10.1038/srep43006

Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

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