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ADAMTS-15 has a tumor suppressor role in prostate cancer

Binder, Marley, McCoombe, Scott, Williams, ED, McCulloch, DR and Ward, Alister 2020, ADAMTS-15 has a tumor suppressor role in prostate cancer, Biomolecules, vol. 10, no. 5, pp. 1-16, doi: 10.3390/biom10050682.

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Title ADAMTS-15 has a tumor suppressor role in prostate cancer
Author(s) Binder, Marley
McCoombe, ScottORCID iD for McCoombe, Scott orcid.org/0000-0001-6717-7511
Williams, ED
McCulloch, DR
Ward, AlisterORCID iD for Ward, Alister orcid.org/0000-0001-7945-7975
Journal name Biomolecules
Volume number 10
Issue number 5
Article ID 682
Start page 1
End page 16
Total pages 16
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2020
ISSN 2218-273X
2218-273X
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
ADAMTS
ECM
prostate cancer
tumor suppressor
VCAN
versikine
METALLOPROTEINASE DOMAIN
EXTRACELLULAR-MATRIX
DISINTEGRIN-LIKE
CELL-MIGRATION
HUMAN BREAST
VERSICAN
EXPRESSION
GROWTH
PROTEOGLYCANS
ACCUMULATION
Summary Extracellular matrix remodeling has emerged as an important factor in many cancers. Proteoglycans, including versican (VCAN), are regulated via cleavage by the proteolytic actions of A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 motif (ADAMTS) family members. Alterations in the balance between Proteoglycans and ADAMTS enzymes have been proposed to contribute to cancer progression. Here, we analyzed the expression of ADAMTS-15 in human prostate cancer, and investigated the effects of enforced expression in prostate cancer cell lines. ADAMTS-15 was found to be expressed in human prostate cancer biopsies with evidence of co-localization with VCAN and its bioactive cleavage fragment versikine. Enforced expression of ADAMTS-15, but not a catalytically-inactive version, decreased cell proliferation and migration of the ‘castrate-resistant’ PC3 prostate cancer cell line in vitro, with survival increased. Analysis of ‘androgen-responsive’ LNCaP prostate cancer cells in vivo in NOD/SCID mice revealed that ADAMTS-15 expression caused slower growing tumors, which resulted in increased survival. This was not observed in castrated mice or with cells expressing catalytically-inactive ADAMTS-15. Collectively, this research identifies the enzymatic function of ADAMTS-15 as having a tumor suppressor role in prostate cancer, possibly in concert with androgens, and that VCAN represents a likely key substrate, highlighting potential new options for the clinic.
Language eng
DOI 10.3390/biom10050682
Indigenous content off
Field of Research 0601 Biochemistry and Cell Biology
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136557

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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