Microvessel density in tumor section

Over the last decades numerous factors involved in the development and progression of some solid human cancers have been identified. Among these, tumour angiogenesis is certainly one the most important owing to the fact that, in order to grow and to develop, a tumour needs to be supplied with a vascular system following its growth. Furthermore, many clinical studies have shown that neovascularization is strictly connected with the surge of metastases and with a worse prognosis in various types of human tumours, and also with more advanced pre-invasive dysplastic lesions. Thus, angiogenesis can represent a useful marker for tumour prognosis and diagnosis.

 Angiogenesis is a complex process involving not only endothelial cell proliferation but also the digestion of the extracellular matrix surrounding the capillaries by collagenases and proteases with consequent endothelial cell migration and new capillaries differentiation. The multistep process requires the interaction of numerous factors able to stimulate the growth and development of new vessels. This may occur either directly, by activating the endothelial cells or promoting enzyme syntesis for the release of angiogenetic factors, or indirectly, by stimulating the stromal cells to produce enzymes (stromelysine, collagenases) that cause the degradation of the extracellular matrix and induce angiogenesis, thus facilitating the release of endothelial cells.

 Recent studies have highlighted the correlation between angiogenetic factors and tumour neovascularization, and also the possibility for these factors to play a predictive role in tumour prognostic evaluation. The significance of neoangiogenesis in the different stages of some tumor models has been further investigated. This suggest the need to study the problem of preinvasive lesions of some neoplasias (not only with regard to quantification but also to its regulation by angiogenetic factors).

 As the angiogenetic process is regulated both by specific growth factors and also some suppressor genes, we are induced to study the existing relationship between angiogenesis and tissue expression of some suppressor genes such as protein p53.

 This project is based on angiogenesis studies which have been already performed in our laboratory. Its aim is to analyze the following aspects:

 1) role of neovascularization in the prognostic evaluation of non small cell lung carcinomas, in prostate and head and neck carcinomas;

2) expression of angiogenetic factors in non small cell lung cancer, prostate and head and neck carcinomas;

3) correlation between tissue expression and serum levels of angiogenetic factors and intratumoral density of neovascularization;

4) correlation between the expression of angiogenetic factors and prognosis;

5) study of angiogenesis in the different stages of bronchial and mammary tumorigenesis;

6) study of the correlation between intratumoral angiogenesis and expression of p53 cellular accumulation;

The project will be divided into different parts starting with the investigations which use already implemented and standardised methods. Concomitantly, all the methods necessary to increase the molecular knowledge of the various problems (PCR, in situ hybridization) for completion of the investigations will be performed.