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|Authors: ||Lualdi, Marta|
|Internal Tutor: ||TARAMELLI, ROBERTO|
|Co-tutor: ||ACQUATI, FRANCESCO|
|Title: ||Functional analysis of the human RNASET2 gene: non-cell autonomous tumor suppression and putative stress-induced cell autonomous boles.|
|Abstract: ||RNASET2 is an atypical tumor suppressor gene, which behaves as a member of the "tumor antagonizing/malignancy suppressor genes" class. Indeed, in our recent works we have demonstrated that RNASET2 overexpression in ovarian cancer cells is associated with a strong suppression of their tumorigenicity in vivo, without affecting any in vitro cancer-related growth parameter. Noteworthy, the control of tumor growth apparently relies on a non-cell autonomous mechanism which involves the establishment of a cross-talk between RNASET2-overexpressing cancer cells and the tumor microenvironment, where the monocyte/macrophage lineage turned out to represent the most likely target of RNASET2 activity.
Within this framework, the principal aim of my Ph.D. project was to investigate the putative occurrence of a functional cross-talk between the RNASET2-overexpressing tumor cell and the innate immune target cells.
I demonstrate here that RNASET2 protein binds the monocyte/macrophage cell surface via a receptor-mediated interaction and exerts a chemotactic activity on this cell lineage. Thus, I propose that the recruitment and the functional activation of such cells within the tumor microenvironment could be responsible for the RNASET2-mediated tumor suppression that occurs in vivo.
Moreover, I present here data demonstrating both the overexpression and sub-cellular re-localization of RNASET2 protein in response to different stress-inducing treatments. Thus, as for other members of the T2 ribonucleases family, I propose that human RNASET2 could play a cell autonomous role in orchestrating defense mechanisms against stress conditions.
Collectively, these data suggest that at the tumor microenvironment level human RNASET2 could act as an "alarmin", both overexpressed and secreted during the early stages of tumor progression in order to activate innate immune defense mechanisms against the tumor.|
|Keywords: ||Tumor suppressor genes, tumor microenvironment, cellular stress, ovarian carcinoma.|
|Issue Date: ||2012|
|Doctoral course: ||Biotecnologie|
|Academic cycle: ||25|
|Publisher: ||Università degli Studi dell'Insubria|
|Citation: ||Lualdi, M.Functional analysis of the human RNASET2 gene: non-cell autonomous tumor suppression and putative stress-induced cell autonomous boles. (Doctoral Thesis, Università degli Studi dell'Insubria, 2012).|
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