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Supplementary Figure 7 from Matrix Metalloproteinase-9 Is Upregulated in Nucleophosmin-Anaplastic Lymphoma Kinase–Positive Anaplastic Lymphomas and Activated at the Cell Surface by the Chaperone Heat Shock Protein 90 to Promote Cell Invasion

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posted on 2023-03-30, 19:51 authored by Frédéric Lagarrigue, Sophie Dupuis-Coronas, Damien Ramel, Georges Delsol, Hélène Tronchère, Bernard Payrastre, Frédérique Gaits-Iacovoni
Supplementary Figure 7 from Matrix Metalloproteinase-9 Is Upregulated in Nucleophosmin-Anaplastic Lymphoma Kinase–Positive Anaplastic Lymphomas and Activated at the Cell Surface by the Chaperone Heat Shock Protein 90 to Promote Cell Invasion

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ARTICLE ABSTRACT

Many anaplastic large cell lymphomas (ALCL) express the chimeric oncogene NPM-ALK, which drives malignant transformation and invasion. In this study, we show that NPM-ALK expression increases matrix metalloproteinase-9 (MMP-9) expression. Accordingly, we found that 100% of a large panel of ALK(+) ALCL biopsies examined were also MMP-9(+), in contrast to only 36.3% of ALK(−) tumors. Mechanistic studies revealed that Rac1 drove MMP-9 secretion. The MMP inhibitor GM6001 and MMP-9 blocking antibodies abolished the invasiveness of NPM-ALK(+) cells. Interestingly, the hyaluronan receptor CD44 acted as a docking surface for MMP-9 and the chaperone heat shock protein 90 on the cell surface, where MMP-9 was cleaved and activated. Membrane-associated MMP-9 was localized to invadopodia, which display a strong gelatinase activity. Taken together, our observations strengthen the concept that chaperones have a major extracellular role in the regulation of protein activation status, and reveal new factors that are crucial for spreading and invasion of ALK(+) ALCL. They also point out new factors crucial for ALK(+) ALCL. Cancer Res; 70(17); 6978–87. ©2010 AACR.