期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 21, 期 12, 页码 3741-3751出版社
WILEY
DOI: 10.1111/jcmm.13283
关键词
MMP-2; MMP-13; large cell lung cancer; vasculogenic mimicry; laminin5
资金
- Key project of the National Natural Science Foundation of China [81230050]
- National Natural Science Foundation of China [81172046, 81173091, 81201791]
- Key project of the Tianjin Natural Science Foundation [12JCZDJC23600]
- Tianjin Natural Science Foundation [12JCYBJC23600]
- Natural Science Foundation of Tianjin Education Commission [20120103]
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 VM, Ln-5 and EGFR in LCLC tissues and xenograft. In vivo experiments revealed that VM was decreased when the number of endothelium-dependent vessels (EDVs) increased during xenograft tumour growth, whereas MMP-13 expression was progressively increased. In conclusion, MMP-2 promoted and MMP-13 disrupted VM formation in LCLC by cleaving Ln-5 to influence EGFR signal activation. MMP-13 may regulate VM and EDV formation.
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