MMP‐2 and MMP‐13 affect vasculogenic mimicry formation in large cell lung cancer

摘要

Matrix metalloproteinases (MMPs) have critical functions in tumour vasculogenic mimicry (VM). This study explored the mechanisms underlying MMP‐13 and MMP‐2 regulation of tumour VM formation in large cell lung cancer (LCLC). In our study, laminin5 (Ln‐5) fragments cleaved by MMP‐2 promoted tubular structure formation by the LCLC cell lines H460 and H661 in three‐dimensional (3D) cultures. Transient up‐regulation of MMP‐13 or treatment with recombinant MMP‐13 protein abrogated tubular structure formation of H460 cells in 3D culture. Treated cells with Ln‐5 fragments cleaved by MMP‐2 stimulated EGFR and F‐actin expression. Ln‐5 fragments cleaved by MMP‐13 decreased EGFR/F‐actin expression and disrupted VM formation. MMP‐13 expression was negatively correlated with style="fixed-case">VM, Ln‐5 and style="fixed-case">EGFR in style="fixed-case">LCLC tissues and xenograft. In vivo experiments revealed that style="fixed-case">VM was decreased when the number of endothelium‐dependent vessels ( style="fixed-case">EDVs) increased during xenograft tumour growth, whereas style="fixed-case">MMP‐13 expression was progressively increased. In conclusion, style="fixed-case">MMP‐2 promoted and style="fixed-case">MMP‐13 disrupted style="fixed-case">VM formation in style="fixed-case">LCLC by cleaving Ln‐5 to influence style="fixed-case">EGFR signal activation. style="fixed-case">MMP‐13 may regulate style="fixed-case">VM and style="fixed-case">EDV formation.