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Human NK cell lines migrate differentially in vitro related to matrix interaction and MMP expression
Author(s) -
Edsparr Karin,
Johansson Bengt R,
Goldfarb Ronald H,
Basse Per H,
Nannmark Ulf,
Speetjens Frank M,
Kuppen Peter JK,
Lennernäs Bo,
Albertsson Per
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.35
Subject(s) - matrigel , podosome , invadopodia , matrix metalloproteinase , extracellular matrix , microbiology and biotechnology , cell culture , in vitro , biology , matrix (chemical analysis) , immunology , cell , chemistry , biochemistry , genetics , cytoskeleton , chromatography , cancer , cancer cell
Matrix metalloproteinases (MMPs) are thought to be of importance for the migratory ability of natural killer (NK) cells. Their expression and production may influence the amount of tumour‐infiltrating NK cells and thereby any therapeutic capability. In this study, we sought to investigate the importance of MMPs for human NK cells’ ability to degrade and migrate through the extracellular matrix (ECM). The two human NK cell lines, NK‐92 and YT, migratory ability, MMP expression and production as well as their morphological appearance when cultured in the ECM equivalent Matrigel were analysed and compared. The quantitatively more migratory NK‐92 cells were found to express invadopodia/podosomes at a significantly higher degree when cultured in Matrigel and gave rise to a general disintegration of the Matrigel. The NK‐92 cells had a higher mRNA expression of MMP‐2, ‐9, ‐13, MT1‐, MT3‐ and MT6‐MMP and a significantly higher production of MMP‐9 compared to YT cells. These differences could explain the substantial functional difference observed between the two cell lines with respect to migratory capacity. In addition, the number of Matrigel invading NK‐92 cells decreased significantly in the presence of the MMP inhibitor GM6001, demonstrating that MMPs have a critical function in their migration.