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Contents - College of Medical and Dental Sciences - University of ...

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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK<br />

Poster Session Abstract P5<br />

ENDOTHELIAL PROGENITORS FROM THE PERIPHERAL BLOOD OF PATIENTS<br />

WITH CLASSIC KAPOSI’S SARCOMA ARE PERSISTENTLY INFECTED BY KSHV<br />

Taddeo A 1 , Della Bella S, 1 Colombo E, 1 Brambilla L, 2 Bergamo E, 3 Calabrò ML. 3<br />

1Laboratory <strong>of</strong> Immunology, Dipartimento di Scienze e Tecnologie Biomediche, Università<br />

degli Studi di Milano; 2 Departiment di Dermatology, IRCCS Ospedale Maggiore,<br />

Milano; 3 Immunology <strong>and</strong> Diagnostic Molecular Oncology, Istituto Oncologico Veneto,<br />

IRCCS, Padova, Italy.<br />

Abstract<br />

Accumulating evidence indicates that tumor angiogenesis is supported by the<br />

mobilization <strong>and</strong> incorporation <strong>of</strong> endothelial progenitor cells (EPCs), highly proliferative<br />

precursors <strong>of</strong> bone marrow origin. Our recent demonstration that EPCs are increased in<br />

the peripheral blood <strong>of</strong> patients with Kaposi’s sarcoma (KS), together with the intrinsic<br />

biologic properties <strong>of</strong> these cells, strongly suggests that EPCs could be involved in the<br />

pathogenesis <strong>of</strong> KS. The fact that the characteristic spindle cells share many markers<br />

with vascular endothelial cells <strong>and</strong> are thought to be <strong>of</strong> endothelial origin further supports<br />

this hypothesis. A possible scenario may be that EPCs may act as preferential KSHV<br />

reservoirs <strong>and</strong>, whether infected, may home to permissive sites <strong>and</strong> propagate to<br />

produce KS lesions. Novel insights into the state <strong>of</strong> KSHV infection <strong>of</strong> EPCs could greatly<br />

improve the comprehension <strong>of</strong> KS pathogenesis. Therefore, we investigated KSHV<br />

infection <strong>of</strong> ex-vivo cultured late-EPCs that, among other cell populations with endothelial<br />

features, contribute more directly to neovascularization <strong>and</strong> might represent a major<br />

source <strong>of</strong> endothelial progenitors in vivo. We found that late-EPCs from KS patients<br />

harbor KSHV DNA <strong>and</strong> retain the virus after multiple passages. Lytic phase induction or<br />

hypoxia could amplify the virus in cells <strong>and</strong> supernatants, indicating that late-EPCs<br />

support KSHV productive replication. EPCs appear therefore to represent potential virus<br />

reservoirs <strong>and</strong> putative precursors <strong>of</strong> KS spindle cells. The biological mechanisms that<br />

govern the infection <strong>of</strong> EPC by KSHV are currently under investigation.<br />

Presenting author Email: lcalabro@unipd.it<br />

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