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Polytechnic University of Marche; Protein cross-talk regulates mesothelial cancer cell proliferation

Posted on: Thursday, 26 February 2004, 06:00 CST

2004 MAR 3 - (NewsRx.com & NewsRx.net) -- Protein cross-talk regulates mesothelial cancer cell proliferation.

According to a study from Italy, "vascular endothelial growth factor (VEGF) and semaphorin-3A (Sema-3A) play important roles in the transduction of promitotic and antimitotic signals, respectively. Here, we report that these conflicting signals are integrated via negative feedback between VEGF and Sema-3A pathways in several primary normal, but not malignant, mesothelial cells. Unlike malignant mesothelial (MM) cells, in which VEGF induces cell proliferation, normal mesothelial (NM) cell growth was repressed by VEGF."

"Although both cell-types expressed an overlapping set of VEGF tyrosine-kinase receptors, only in NM cells VEGF exposure entails a p38 mitogen-activated protein kinase (MA-PK)-dependent increased of Sema-3A production. Inhibition of p38 MAPK (by SB202190 and SB203580) or a dominant-negative mutant of Sema-3A receptor plexin- Al reversed the inhibitory effects of VEGF in NM cells, increasing cyclin D1 synthesis and cell growth," reported A. Catalano and colleagues, Polytechnic University of Marche, Department of Molecular Pathology and Innovative Therapy.

"Conversely, sustained activation of p38 MAPK by the p38 MAPK- activating kinases MKK3 and MKK6 or transfection with Sema-3A inhibited VEGF-induced cyclin D1 upregulation and MM cell proliferation. Therefore, these results delineate a new role of Sema- 3A in VEGF function mediated by p38 MAPK and suggest that the abrogation of regulated Sema-3A expression is responsible for VEGF- driven growth of tumor cells," researchers concluded.

Catalano and colleagues published the results of their research in FASEB Journal (Cross-talk between vascular endothelial growth factor and semaphorin-3A pathway in the regulation of normal and malignant mesothelial cell proliferation. FASEB J, 2003;17(15):U495- U514).

For additional information, contact A. Catalano, University Politecn Marche, Dipartimento Patol Molecular & Terapie Innovat, Via Ranieri 6, I-60131 Ancona, Italy.

The publisher of the FASEB Journal can be contacted at: Federation of the American Society for Experimental Biology, 9650 Rockville Pike, Bethesda, MD 20814-3998, USA.

The information in this article comes under the major subject areas of Angiogenesis and Oncology.

This article was prepared by Biotech Week editors from staff and other reports. Copyright 2004, Biotech Week via NewsRx.com & NewsRx.net.

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