Characterization of neoplastic and non-neoplastic microenvironment in liver, lung and bone marrow through the study of class III β-tubulin

The following PhD thesis on Human Oncological Pathology and Stem Cell is focused on class III beta-tubulin (tubb3) that has been mainly investigated in oncological context for epithelial tumors as a marker of resistance to taxane and aggressiveness. Recently it has also been described as marker for pericytes, Recentemente è stata poi descritta come marker dei pericytes, which are cells indicating the maturity of vessels but have also contractility properties and morphologically recalls myofibroblasts. The presence of tubb3 in rare cases of hepatocellular carcinoma, differently compared to other carcinomas e the peculiar positivity in newly formed tumoral vessels, has suggested the possible wide potentiality of this marker compared to what has already been described in literature. For this reason we have decided to develop 3 projects in parallel on different diseases, both non-neoplastic (idiopathic pulmonary fibrosis) and neoplastic (hepatocellular carcinoma and primary myelofibrosis) conditions, that are in a way accumunated by the presence of a spindle population of cells resembling myofibroblasts. In pulmonary fibrosis, tubb3 identify the myofibroblasts forming fibroblastic foci, that are a pathognomonic lesion of the disease. This study has produced an original article that has been submitted. In Hepatocellular carcinoma, tubb3 is found only rarely in neoplastic cells, often at the front of edge of the tumor and in 1/3 of cases in peritumoral and intratumoral vessels. The peculiarity of these results has driven the idea of another study on dynamic 3D-cultures with Bioreactor, to investigate how tumoral vessels behave in dynamic cultures also when they are subjected to drug, such as Sorafenib. This study is on-going with the group of Tumor Microenvironment of ’Ospedale San Raffaele in Milano, where the Bioreactor is available. Concerning primary myelofibrosis, it was the name of the disease that suggested us to investigate this process with tubb3. Thank to the intial encouraging results, we have initiated a collaboration with the the Department of Haematology of Policlinico GB Rossi in Verona to understand id the patients that present a tubb3 positive population in the context of bone marrow biopsy have a different type of disease compared to other myelofibrosis and if this heterogeneity has some relation to mutational status.