Abstract
Proteins secreted in the extracellular matrix microenvironment (ECM) by tumor cells are involved in cell adhesion, motility, intercellular communication and invasion. The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-ECM interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been implicated in tissue remodeling events observed in cancer development, growth and progression. Here we investigated the subcellular localization of ADAMTS-1 in normal-like (MCF10-A) and tumoral (MCF7 and MDA-MB-231) human breast cells. ADAMTS-1 is a secreted protease found in the extracellular matrix. However, in this study we show for the first time that ADAMTS-1 is also present in the nuclei and nucleoli of the three mammary cell lines studied here. Our findings indicate that ADAMTS-1 has proteolytic functions in the nucleus through its interaction with aggrecan substrate.
Highlights
The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-extracellular matrix (ECM) interactions and in the generation of new signals from the cell surface
Metalloproteinases belonging to the ADAMTS family have been widely implicated in tissue remodeling events observed in cancer development, growth and progression [1]
The negative control using irrelevant IgG is shown in S1B Fig. In HT1080, a cell line derived from fibrosarcoma, ADAMTS-1 is present mainly in the cytoplasm (S1C Fig)
Summary
The tumor microenvironment is expansively modified and remodeled by proteases, resulting in important changes in both cell-cell and cell-extracellular matrix (ECM) interactions and in the generation of new signals from the cell surface. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been widely implicated in tissue remodeling events observed in cancer development, growth and progression [1]. The ADAMTS proteinases belong to a family of metalloproteinases that have extracellular matrix processing, organogenesis, and hemostasis functions. They are involved in remodeling of the extracellular matrix in physiological processes as well as in pathological states, including cancer [1]. ADAMTS4 and ADAMTS-5 are multi-domain metalloproteases secreted into the extracellular space. They both have a catalytic metalloprotease domain and a series of other ancillary domains regulating activity and substrate specificity [4]
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