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Aptamer-mediated impairment of EGFR-integrin alphavbeta3 complex inhibits vasculogenic mimicry and growth of triple-negative breast cancers (64 visite) (PDF 94 visite)
Sci Rep (ISSN: 2045-2322electronic, 2045-2322linking), 2017 Apr 20; 7: 46659-46659.
Tipo di articolo: Journal Article,
Impact factor: 4.259
Impact factor a 5 anni: 4.847
Parole chiave: Non disponibili.
Url: Non disponibile.
Current treatment options for triple-negative breast cancers (TNBCs) is limited by the absence of well-defined biomarkers, excluding a targeted therapy. Notably, epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of TNBCs and is a negative prognostic factor. In clinical trials, however, existing EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a valid alternative to antibodies for diagnostic and therapeutic uses. Here, we prove that, when applied to aggressive TNBC cell lines with unique stem-like plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents the vasculogenic mimicry (VM) capability of the cells and destroys previously formed channels in three-dimensional culture. Notably, we found that CL4 impairs the matrix-induced integrin alphavbeta3 interaction with EGFR and integrin alphavbeta3-dependent cell adhesion. Consistently, the aptamer strongly inhibits VM and tumor growth in a xenograft TNBC model. These data suggest that in TNBC cells, EGFR may cooperate with integrin alphavbeta3 to regulate integrin binding to extracellular ligands required for VM, and EGFR-targeting by CL4 aptamer may counteract this event. Overall, we demonstrate a novel mechanism of action for CL4 related with integrin alphavbeta3-EGFR interaction, that may help to develop new oligonucleotide-based strategy addressing unmet need for TNBCs therapy.
*** IBB - CNR ***
Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore" (IEOS), Consiglio Nazionale delle Ricerche (CNR), Via S. Pansini 5, 80131 Naples, Italy., Istituto di Biostrutture e Bioimmagini (IBB), Consiglio Nazionale delle Ricerche (CNR), Via T. De Amicis 95, 80145 Naples, Italy.,
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