ADAMTS-1 has nuclear localization in cells with epithelial origin and leads to decreased cell migration.

In the study of tumorigenesis, the involvement of molecules within the extracellular matrix (ECM) is crucial. ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin motifs), a group of secreted proteases known for their role in ECM remodeling, were primarily considered to be extracellular proteases. However, our research specifically detected ADAMTS-1, a member of this family, predominantly within the nucleus of mammary cells. Our main objective was to understand the mechanism of ADAMTS-1 translocation to the nucleus and its functional significance in this cellular compartment. Our investigation uncovered that nuclear ADAMTS-1 was present in cells exhibiting an epithelial phenotype, while cells of mesenchymal origin contained the protease in the cytoplasm. Moreover, disruption of ADAMTS-1 secretion, induced by Monensin treatment, resulted in its accumulation in the cytoplasm. Notably, our research indicated that alterations in the secretory pathways could influence the protease's compartmentalization. Additionally, experiments with conditioned medium from cells containing nuclear ADAMTS-1 demonstrated its internalization into the nucleus by HT-1080 cells and fibroblasts. Furthermore, heightened levels of ADAMTS-1 within the ECM reduced the migratory potential of mesenchymal cells. This highlights the potential significance of nuclear ADAMTS-1 as a critical component within the tumor microenvironment due to its functional activity in this specific cellular compartment.

Progesterone decreases ovarian cancer cells migration and invasion.

The progression of cancer depends on the interaction between the cells and their microenvironment. Progesterone is a steroid and progestogen sex hormone produced by the corpus luteum, which is a transitory endocrine gland in female mammals and prepares the endometrium for implantation. Also, progesterone is involved in antitumorigenic process in different types of cancer. Our goal is to investigate the role of progesterone in cell invasion and migration. Ovarian cells were treated with different concentrations of progesterone. 500 nM or 1 µM progesterone decreased the migration of the cells in 24 h or less without affecting the viability. Immunoblot showed that treatment with 1 µM progesterone decreased the phosphorylated forms of Src and FAK, and the cells were less polarized. Our results suggest that progesterone interferes with migration and invasion of ovarian cells. Inhibitory experiments inferred the progesterone receptor playing a role in migration and invasion. Decreased phosphorylation of molecules involved in these processes was also found.

Laminin-derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells.

Laminin peptides influence cancer biology. We investigated the role of a laminin-derived peptide C16 regulating invadopodia molecules in human prostate cancer cells (DU145). C16 augmented invadopodia activity of DU145 cells, and stimulated expression Tks4, Tks5, cortactin, and membrane-type matrix metalloproteinase 1. Reactive oxygen species generation is also related to invadopodia formation. This prompted us to address whether C16 would induce reactive oxygen species generation in DU145 cells. Quantitative fluorescence and flow cytometry showed that the peptide C16 increased reactive oxygen species in DU145 cells. Furthermore, significant colocalization between Tks5 and reactive oxygen species was observed in C16-treated cells. Results suggested that the peptide C16 increased Tks5 and reactive oxygen species in prostate cancer cells. The role of C16 increasing Tks and reactive oxygen species are novel findings on invadopodia activity.

ADAMTS-1 Is Found in the Nuclei of Normal and Tumoral Breast Cells.

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.

Progesterone acts via the progesterone receptor to induce adamts proteases in ovarian cancer cells.

BACKGROUND: Ovarian carcinomas, usually associated with sex hormones dysregulation, are the leading cause of gynecological neoplastic death. In normal ovaries, hormones play a central role in regulating cell proliferation, differentiation, and apoptosis. On the other hand, hormonal alterations also play a variety of roles in cancer. Stimulation by sex hormones potentially affects gene expression, invasiveness, cell growth and angiogenesis. Proteases of the "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) family are secreted by different cell types and become involved in collagen processing, cleavage of the proteoglycan matrix, and angiogenesis. We evaluated whether sex hormones affect ADAMTS 1 and 4 expression in ovarian cancer cells. METHODS: We analysed mRNA and protein levels in human ovarian tumor cells with different degrees of malignancy, NIH-OVCAR-3 and ES-2, that were treated or not with estrogen, testosterone and progesterone. RESULTS: Our results suggest that progesterone increases ADAMTS protein and mRNA levels in the lysates from ES-2 cells, and it increases ADAMTS protein in the lysates and conditioned media from NIH-OVCAR-3. Progesterone effects were reversed by RU486 treatment. CONCLUSION: We conclude that progesterone acts via the progesterone receptor to modulate ADAMTS 1 and 4 levels in ovarian cancer cell lines.