Evidence map›Paper›PMID 42332735›Full record

ArticleJournal of biomedical science2026

Enhanced expression of ADAMTS1 in ovarian carcinomas: loss of ADAMTS1 expression instigates cellular reprogramming of extracellular matrix ensuing altered plasticity, augmented migration and attenuated adhesion.

Ruth M Escalona, Dylan King, Noor A Lokman, Martin K Oehler, Carmela Ricciardelli, George Kannourakis, Nuzhat Ahmed

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Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Ruth M EscalonaFiona Elsey Cancer Research Institute, Suites 23, 106-110 Lydiard Street South, Ballarat Technology Park Central, Ballarat, VIC 3353, Australia.
Dylan KingFiona Elsey Cancer Research Institute, Suites 23, 106-110 Lydiard Street South, Ballarat Technology Park Central, Ballarat, VIC 3353, Australia.
Noor A LokmanSchool of Medicine, College of Health, Adelaide University, Adelaide, SA 5000, Australia.
Martin K OehlerSchool of Medicine, College of Health, Adelaide University, Adelaide, SA 5000, Australia.
Carmela RicciardelliSchool of Medicine, College of Health, Adelaide University, Adelaide, SA 5000, Australia.
George KannourakisFiona Elsey Cancer Research Institute, Suites 23, 106-110 Lydiard Street South, Ballarat Technology Park Central, Ballarat, VIC 3353, Australia.
Nuzhat AhmedFiona Elsey Cancer Research Institute, Suites 23, 106-110 Lydiard Street South, Ballarat Technology Park Central, Ballarat, VIC 3353, Australia. nuzhata@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundADAMTS1, a disintegrin and metalloproteinase with thrombospondin motif 1, plays a role in inflammation, organogenesis, and ovulation. Up or downregulation of ADAMTS1 has been implicated in tissue remodelling leading to cancer. We analysed the expression of ADAMTS1 in different stages/grades of primary and metastatic serous ovarian tumours and ascites-derived tumour cells from patients and assessed the functional role of ADAMTS1 in ovarian cancer (OC) cell lines.

methodsThe expression and localisation of ADAMTS1 was assessed by immunohistochemistry (IHC) and Opal Multiplex IHC staining of OC tissues. Functional roles of ADAMTS1 in OC cell lines were assessed by using siRNA-mediated knockdown (KD), MTT assay, cell migration by xCELLigence, cell adhesion, ELISA, qRT-PCR, Western blot, immunofluorescence (IF) and activity of Cdc42 GTPase.

resultsThe expression of ADAMTS1 was significantly enhanced in higher stages/grades of ovarian tumours compared to benign tumours. In high-grade tumours, ADAMTS1 was localised more in the nucleus of epithelial cells while localisation in stromal cells was mostly in the cytoplasm. Significantly higher mRNA expression of ADAMTS1 was noted in epithelial compared to mesenchymal ascites-derived tumour cells. The expression of ADAMTS1 was significantly higher in metastatic high-grade tumours compared to primary tumours. KD of ADAMTS1 expression by siRNA in OC cell lines had no effect on cell proliferation but resulted in decreased cell adhesion, increased cell migration accompanied by increased expression of markers (CDH1 and EPCAM) associated with epithelial plasticity. Remodelling of ECM accompanied by increased intra- and extracellular production of VCAN and enhanced Cdc42 GTPase activity was also noted in cell lines with ADAMTS1 KD. Cdc42 GTPase specific inhibitor, ML141, reversed ADAMTS1 KD-mediated enhanced migration. On the other hand, VCAN KD inhibited ADAMTS1 KD-mediated migration and reversed the effect on cell adhesion.

conclusionsThese results suggest that the expression of ADAMTS1 progressively enriches ovarian tumours and promotes OC progression. Its knock down in in vitro cell culture impacts ECM remodelling through enhanced Cdc42GTPase activity and VCAN production resulting in epithelial cell plasticity, accelerated migration, and reduced cell adhesion.

Indexed as

ADAMTS1 ProteinCell AdhesionCell MovementExtracellular MatrixGene Expression Regulation, NeoplasticOvarian NeoplasmsCell Line, TumorFemaleHumansADAMTS1 ProteinADAMTS1 protein, humanADAMTS1AdhesionCdc42Cellular plasticityMETMigrationMMP9Ovarian cancerProliferationVersican

Identifiers

PMID42332735
PMCPMC13289130

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