Abstract
Sarcomas are deadly malignant tumors of mesenchymal origin occurring at all ages. The expression and function of the membrane-type matrix metalloproteinase MMP14 is closely related to the mesenchymal cell phenotype, and it is highly expressed in most sarcomas. MMP14 regulates the activity of multiple extracellular and plasma membrane proteins, influencing cell–cell and cell–extracellular matrix (ECM) communication. This regulation mediates processes such as ECM degradation and remodeling, cell invasion, and cancer metastasis. Thus, a comprehensive understanding of the biology of MMP14 in sarcomas will shed light on the mechanisms controlling the key processes in these diseases. Here, we provide an overview of the function and regulation of MMP14 and we discuss their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas.
Highlights
Sarcomas are a heterogeneous and deadly group of mesenchymal malignancies that are relatively rare, accounting for
In undifferentiated pleomorphic sarcoma (UPS), MMP2 and MMP9 protein expression and activity are higher in malignant tissues than in the normal counterparts, and both the pro- and active forms of MMP2 are increased in metastatic compared to non-metastatic patients [67]
Hypermethylated MMP14 and MMP2 promoters have been found in the non-invasive MCF7 breast cancer cell lines, whereas highly migratory glioma cells display hypomethylated promoters coupled to high MMP14 and MMP2 expression levels [100,101]
Summary
Sarcomas are a heterogeneous and deadly group of mesenchymal malignancies that are relatively rare, accounting for
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