Abstract
High expression of immunoglobulin G (IgG) in many non-B cell malignancies and its non-conventional roles in promoting proliferation and survival of cancer cells have been demonstrated. However, the precise function of non-B IgG remains incompletely understood. Here we define the antigen specificity of RP215, a monoclonal antibody that specifically recognizes the IgG in cancer cells. Using RP215, our study shows that IgG is overexpressed in cancer cells of epithelial lineage, especially cells with cancer stem/progenitor cell-like features. The RP215-recognized IgG is primarily localized on the cell surface, particularly lamellipodia-like structures. Cells with high IgG display higher migration, increased invasiveness and metastasis, and enhanced self-renewal and tumorgenecity ability in vitro and in vivo. Importantly, depletion of IgG in breast cancer leads to reduced adhesion, invasion and self-renewal and increased apoptosis of cancer cells. We conclude that high expression of IgG is a novel biomarker of tumor progression, metastasis and cancer stem cell maintenance and demonstrate the potential therapeutic benefits of RP215-recognized IgG targeted strategy.
Original language | English (US) |
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Pages (from-to) | 40081-40094 |
Number of pages | 14 |
Journal | Oncotarget |
Volume | 6 |
Issue number | 37 |
DOIs | |
State | Published - 2015 |
Keywords
- Epithelial stem/progenitor-like cells
- IgG
- RP215
- Tumor metastasis
ASJC Scopus subject areas
- Oncology