Special Project Angiogenesis

Investigator: Giuseppe Viglietto

Title of the project Analysis of the endothelial growth factors PlGF and VEGF as mediators of tumor-associated neoangiogenesis in human thyroid and mammary carcinomas.

Human endothelial cells in culture express Factor VIII-related antigen

List of collaborators

Prof. A. Fusco, Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Reggio Calabria.

Dott.ssa Graziella Persico, IIGB, CNR, Napoli

Description of the project

The aim of the present project is to investigate whether the endothelial growth factor PlGF is angiogenic in vivo and it may contribute to tumor-associated neoangiogenesis in human neoplasms.

We propose:

1) to test the proliferative effect of PlGF, alone or together with VEGF and/or bFGF, on a broad number of endothelial cell (EC) types in vitro, in order to evaluate whether PlGF is able to stimulate DNA synthesis in ECs, and whether there exists an additive and/or a synergistic effect among PlGF, bFGF and VEGF;
2) to determine whether PlGF, alone or together with VEGF and/or bFGF, may act as chemoattractant for EC cells in a Boyden chamber assay;
3) to investigate the possibility that PlGF, alone or together with VEGF and/or bFGF, is able to confer chemoinvasive properties to EC in the Boyden chamber/Matrigel assay;
4) to determine whether PlGF, alone or together with VEGF, is able to stimulate the transcription and the secretion of extracellular matrix proteases such as plasminogen activators and collagenases;
5) to evaluate the in vivo angiogenic potential of PlGF both by the rat cornea assay and by the Matrigel assay.

Finally we propose to investigate the molecular mechanisms that mediate neoangiogenesis during the devolopment of human thyroid, testicular and mammary tumors. To this purpose, we will determine the mRNA and protein expression of VEGF, PlGF and their receptors in thyroid, testicular and mammary carcinomas by a combination of techniques (Northern blot, Western blot, In situ hybridization and Immunostaining). Subsequently, we will detemine the molecular mechanisms that regulate the expression of VEGF and PlGF in thyroid cells.