Publication: Levels of acyl-Coenzyme A synthetase 5 in urothelial cells and corresponding neoplasias reflect cellular differentiation
Authors
Gaisa, Nadine T. ; Reinartz, Andrea ; Schneider, Ursula ; Klaus, Christina ; Heidenreich, Axel ; Jakse, Gerhard ; Kaemmerer, Elke ; Klinkhammer, Barbara Mara ; Knuechel, Ruth ; Gassler, Nikolaus
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Metabolic components like fatty acids and
acyl-Coenzyme A (acyl-CoA) thioesters have been
implicated in the pathogenesis of various tumours. The
activation of fatty acids to acyl-CoAs is catalysed by
long chain acyl-CoA synthetases (ACSLs), and
impairment of ACSL expression levels has been
associated with tumourigenesis and progression. Since
ACSLs have never been investigated in bladder tissues,
the study aims to characterize ACSL expression and
acyl-CoA synthesis in normal and neoplastic bladder
tissues, as well as cell lines. ACSL isoforms 1, 3, 4 and 5
and synthesis of acyl-CoAs were analysed using qRTPCR,
western blot analysis, immunohistochemistry and
lipid mass spectrometry.
In normal urothelium, expression of ACSL1, 3, 4
and 5, with highest levels of ACSL isoform 5 was found.
However, ACSL5 expression was reduced in
corresponding neoplastic tissues and urothelial cell lines
depending on the grade of cellular differentiation. AntiACSL5
immunostainings showed expression in normal
urothelium and a gradual loss of ACSL5 protein via preinvasive
lesions to invasive carcinomas. High expression
of ACSL5 correlated with increased α-galactosidase
activity and positive Uroplakin III staining in tumours.
In contrast, synthesis of acyl-CoAs was enhanced in
neoplastic bladder tissues compared to normal
urothelium, and reflected an increase with respect to
cellular differentiation. These results confirm an
expression of ACSLs, especially isoform 5, in human
urothelium, prove enzymatic/lipidomic changes in
bladder cancer tissues, and suggest an involvement of
ACSL5 in cellular maturation and/or senescence with
possible effects onto induction of tumour formation or
progression. Further work may identify responsible
pathway alterations, and attempting to re-balance the
metabolic equilibrium of the urothelium may offer a
further opportunity for tumour treatment and prevention.
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Citation
Histology and histopathology, Vol. 28, n.º 3 (2013)
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