Next Article in Journal
Culture and Differentiation of Human Hair Follicle Dermal Papilla Cells in a Soft 3D Self-Assembling Peptide Scaffold
Next Article in Special Issue
Erratum: Treatment of Dystrophic mdx Mice with an ADAMTS-5 Specific Monoclonal Antibody Increases the Ex Vivo Strength of Isolated Fast Twitch Hindlimb Muscles. Biomolecules 2020, 10, 416
Previous Article in Journal
Advances in Ginsenosides
Previous Article in Special Issue
The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases
Article

ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer

1
School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
2
Centre for Molecular and Medical Research, Deakin University, Waurn Ponds, VIC 3216, Australia
3
Australian Prostate Cancer Research Centre–Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Translational Research Institute, Brisbane, QLD 4102, Australia
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(5), 682; https://doi.org/10.3390/biom10050682
Received: 25 March 2020 / Revised: 23 April 2020 / Accepted: 25 April 2020 / Published: 28 April 2020
(This article belongs to the Special Issue New Insights on ADAMTS Proteases in Health)
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. View Full-Text
Keywords: ADAMTS; ECM; prostate cancer; tumor suppressor; VCAN; versikine ADAMTS; ECM; prostate cancer; tumor suppressor; VCAN; versikine
Show Figures

Figure 1

MDPI and ACS Style

Binder, M.J.; McCoombe, S.; Williams, E.D.; McCulloch, D.R.; Ward, A.C. ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer. Biomolecules 2020, 10, 682. https://doi.org/10.3390/biom10050682

AMA Style

Binder MJ, McCoombe S, Williams ED, McCulloch DR, Ward AC. ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer. Biomolecules. 2020; 10(5):682. https://doi.org/10.3390/biom10050682

Chicago/Turabian Style

Binder, Marley J., Scott McCoombe, Elizabeth D. Williams, Daniel R. McCulloch, and Alister C. Ward. 2020. "ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer" Biomolecules 10, no. 5: 682. https://doi.org/10.3390/biom10050682

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop