Induction of Urokinase Activity by Retinoic Acid in Two Cell Lines of Neuronal Origin

Horvat, Luka; Madunić, Josip; Grubar, Martina; Antica, Mariastefania; Matulić, Maja (2019) Induction of Urokinase Activity by Retinoic Acid in Two Cell Lines of Neuronal Origin. Biomedicines, 7 (3). ISSN 2227-9059

Preview

PDF - Published Version - article
Available under License Creative Commons Attribution.
Download (15MB) | Preview

Official URL: https://www.mdpi.com/2227-9059/7/3/70

Abstract

Retinoic acid is one of the most well-known agents able to induce differentiation in several types of tumours. Unfortunately, most of the tumours are refractive to the differentiation cues. The aim of this investigation was to analyse the effects of prolonged treatment with retinoic acid on two cell lines of neural origin refractive to differentiation. Cells were also treated with retinoic acid in combination with a poly(ADP-ribosyl) polymerase (PARP) inhibitor because PARP1 is a known chromatin modulator and can influence the process of differentiation. The main methods comprised tumour cell line culturing and treatment ; analysis of RNA and protein expression after cell treatment ; as well as analysis of urokinase activity, migration, and proliferation. Both cell lines continued to proliferate under the prolonged treatment and showed increase in urokinase plasminogen activator activity. Analysis of gene expression and cell phenotype revealed different mechanisms, which only in neuroblastoma H4 cells could indicate the process of epithelial-mesenchymal transition. The data collected indicate that the activity of the urokinase plasminogen activator, although belonging to an extracellular protease, does not necessary lead to epithelial-mesenchymal reprogramming and increase in cell migration but can have different outcomes depending on the intracellular milieu.

Item Type:

Article

Uncontrolled Keywords:

neuroglioblastoma cell line ; glioblastoma ; retinoic acid ; PARP1 ; urokinase ; epithelial-mesenchymal transition

Subjects:

NATURAL SCIENCES > Biology

Divisions:

Division of Molecular Biology

Projects:

Project title	Project leader	Project code	Project type
Notch u diferencijaciji hematopoetskih stanica matica i u razvoju leukemija-NOBLE	Mariastefania Antica	IP-2013-11-7140	HRZZ
UNSPECIFIED	DOK	2014-06-9845	UNSPECIFIED
UNSPECIFIED	UNSPECIFIED	KK01.1.1.01.0008	UNSPECIFIED