Alterations 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: 6.83Hz; glycosylated cells Bmax: 7.35Hz). 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
(0.1μM 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.