Tubular network formation by adriamycin-resistant MCF-7 breast cancer cells is closely linked to MMP-9 and VEGFR-2/VEGFR-3 over-expressions

被引:27
作者
Karroum, Asmae [1 ]
Mirshahi, Pezhman [1 ]
Faussat, Anne-Marie [2 ]
Therwath, Amu [1 ]
Mirshahi, Massoud [1 ]
Hatmi, Mohamed [1 ,3 ]
机构
[1] CRC, UMRS 872, Equipe 18, F-75006 Paris, France
[2] IFR 65, F-75012 Paris, France
[3] Inst Pasteur, Dept Infect & Epidemiol, F-75015 Paris, France
关键词
Tubular network; VEGFR-2/VEGFR-3 receptor subtype; MMP-9; Breast cancer cells MCF-7; MDR1; phenotype; ENDOTHELIAL GROWTH-FACTOR; VASCULAR CHANNEL FORMATION; HUMAN-MELANOMA CELLS; VASCULOGENIC MIMICRY; MATRIX METALLOPROTEINASES; SIGNALING PATHWAYS; FACTOR RECEPTOR-2; VEGF RECEPTORS; P-GLYCOPROTEIN; IN-SITU;
D O I
10.1016/j.ejphar.2012.04.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have previously demonstrated that matrix metalloproteinase-9 (MMP-9) is critical for breast cancer cell migration and is necessary but not sufficient for tubular network formation. Given the important angiogenic activity of vascular endothelial growth factor (VEGF), we investigate here its possible contribution in tubular network formation and its link with MMP-9. Exposure of resistant epithelial breast cancer cells (rMCF-7) to Avastin, a VEGF neutralising antibody, suppresses tubular network formation but not cell migration. However, their exposure to MMP-9 inhibitor markedly decreases both parameters. Besides, the addition of exogenous VEGF or MMP-9 alone or in combination to sensitive parental cells (sMCF-7) or rMCF-7 cells enhances tubular network formation by rMCF-7 cells but not by sMCF-7 cells. The evaluation of the expression levels of VEGF receptor (VEGFR) subtypes shows that sMCF-7 cells express only small quantities of VEGFR-2 and VEGFR-3 compared with rMCF-7 cells that express strong quantities. However, treatment of sMCF-7 cells by phorbol 12-myristate 13-acetate (PMA), a PKC activator, induces both tubular network formation and VEGFR-2/VEGFR-3 over-expressions. Interestingly, exposure of rMCF-7 cells or PMA-treated sMCF-7 cells to the specific inhibitors of VEGFR-2 and VEGFR-3 reduces markedly the tubular network formation. Together, our results demonstrate that the proteolytic enzyme MMP-9 promotes rMCF-7 cell migration and, consequently, tubular network formation through VEGFR-2/VEGFR-3 activation. Understanding of mechanisms involved in vasculogenic mimicry and cell migration related to MMP-9 and VEGF may open new opportunities to improve cancer therapy. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 7
页数:7
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