scholarly journals ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 682 ◽  
Author(s):  
Marley J. Binder ◽  
Scott McCoombe ◽  
Elizabeth D. Williams ◽  
Daniel R. McCulloch ◽  
Alister C. Ward
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Human Prostate ◽  
Matrix Remodeling ◽  
Human Prostate Cancer ◽  
Enzymatic Function

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.

scholarly journals Tissue-specific and androgen-regulated expression of human prostate-specific transglutaminase

1996 ◽  
Vol 315 (3) ◽  
pp. 901-908 ◽  
Author(s):  
Hendrikus J. DUBBINK ◽  
Nicole S. VERKAIK ◽  
Peter W. FABER ◽  
Jan TRAPMAN ◽  
Fritz H. SCHRÖDER ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Human Prostate ◽  
Tissue Type ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell

Transglutaminases (TGases) are calcium-dependent enzymes catalysing the post-translational cross-linking of proteins. In the prostate at least two TGases are present, the ubiquitously expressed tissue-type TGase (TGC), and a prostate-restricted TGase (TGP). This paper deals with the molecular cloning and characterization of the cDNA encoding the human prostate TGase (hTGP). For this purpose we have screened a human prostate cDNA library with a probe from the active-site region of TGC. The largest isolated cDNA contained an open reading frame encoding a protein of 684 amino acids with a predicted molecular mass of 77 kDa as confirmed by in vitro transcription–translation and subsequent SDS/PAGE. The hTGP gene was tissue-specifically expressed in the prostate, yielding an mRNA of approx. 3.5 kb. Furthermore, a 3-fold androgen-induced up-regulation of hTGP mRNA expression has been demonstrated in the recently developed human prostate cancer cell line, PC346C. Other well established human prostate cancer cell lines, LNCaP and PC-3, showed no detectable hTGP mRNA expression on a Northern blot. The gene coding for prostate TGase was assigned to chromosome 3.

scholarly journals Cathepsin E enhances anticancer activity of doxorubicin on human prostate cancer cells showing resistance to TRAIL-mediated apoptosis

2010 ◽  
Vol 391 (8) ◽  
Author(s):  
Atsushi Yasukochi ◽  
Tomoyo Kawakubo ◽  
Seiji Nakamura ◽  
Kenji Yamamoto
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Down Regulation ◽  
Cathepsin E

Abstract We previously described that cathepsin E specifically induces growth arrest and apoptosis in several human prostate cancer cell lines in vitro by catalyzing the proteolytic release of soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from the tumor cell surface. It also prevents tumor growth and metastasis in vivo through multiple mechanisms, including induction of apoptosis, angiogenesis inhibition and enhanced immune responses. Using the prostate cancer cell line PPC-1, which is relatively resistant to cell death by doxorubicin (40–50% cytotoxicity), we first report that a combination treatment with cathepsin E can overcome resistance of the cells to this agent. In vitro studies showed that combined treatment of PPC-1 cells with the two agents synergistically induces viability loss, mainly owing to down-regulation of a short form of the FLICE inhibitory protein FLIP. The enhanced antitumor activity was corroborated by in vivo studies with athymic mice bearing PPC-1 xenografts. Intratumoral application of cathepsin E in doxorubicin-treated mice results in tumor cell apoptosis and tumor regression in xenografts by enhanced TRAIL-induced apoptosis through doxorubicin-induced c-FLIP down-regulation and by a decrease in tumor cell proliferation. These results indicate that combination of cathepsin E and doxorubicin is sufficient to overcome resistance to TRAIL-mediated apoptosis in chemoresistant prostate cancer PPC-1 cells, thus indicating therapeutic potential for clinical use.

scholarly journals A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility “in vitro”

2016 ◽  
Vol 103 ◽  
pp. 215-226 ◽  
Author(s):  
Alessandra Colciago ◽  
Ornella Mornati ◽  
Nicola Ferri ◽  
Luca Franco Castelnovo ◽  
Laura Fumagalli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Human Prostate ◽  
Cancer Cell Proliferation ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell
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