PMID: 11918086Mar 29, 2002Paper

An inhibitor of stress-activated MAP-kinases reduces invasion and MMP-2 expression of malignant melanoma cells

Clinical & Experimental Metastasis
Carsten DenkertSteffen Hauptmann

Abstract

A lot of parallels have been described between invasion of malignant tumor cells and leukocyte movement during inflammatory responses. Concerning these similarities, we investigated the function of cytokine-suppressive anti-inflammatory drugs (CSAIDs), which act via inhibition of stress-activated MAP-kinases, in regulation of expression of proteolytic enzymes and in vitro invasion of malignant melanoma cells. The p38MAPK inhibitor SB203580 reduced matrigel invasion of MeWo cells by 60%, while the MEK-1 inhibitor PD98059 did not have any effect on invasion. Active p38MAPK was detected in MeWo cells by immunoblotting and confocal microscopy. Cells showed a constitutive expression of matrix-metalloproteinase (MMP)-2 as well as tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 mRNAs. Expression of MMP-1 or urokinase-type plasminogen activator (uPA) was not detected by Northern blot. Inhibition of p38MAPK by the specific inhibitor SB203580 resulted in downregulation of MMP-2 mRNA and protein levels as well as gelatinolytic activity, while expression levels of TIMP-1 and TIMP-2 mRNAs were not changed. The specific MEK-1 inhibitor PD98059 did not change expression of MMP-2 or TIMPs. Neither SB203580 nor PD98059 changed prolif...Continue Reading

Citations

Jul 10, 2003·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Farooq A SiddiquiJohn L Francis
Mar 12, 2008·World Journal of Gastroenterology : WJG·Lin-Bo WangJian-Guo Shen
Sep 15, 2011·Pigment Cell & Melanoma Research·Pablo Lopez-Bergami
Apr 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haet Nim LimHye Jin Jung
Mar 25, 2009·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Mizuho Fukunaga-KalabisMeenhard Herlyn
Oct 27, 2009·Expert Opinion on Investigational Drugs·Hae-Young YongAree Moon
Feb 21, 2003·International Journal of Cancer. Journal International Du Cancer·Keiran S M Smalley
Aug 24, 2013·International Journal of Molecular Sciences·Visalini Muthusamy, Terrence J Piva
Mar 25, 2014·The FEBS Journal·Min-Hsi ChiuCheng-Yang Chou

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