Contents - College of Medical and Dental Sciences - University of ...
Contents - College of Medical and Dental Sciences - University of ...
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 />
Pathogenesis Abstract 21<br />
DOWNREGULATION OF GALECTIN-3 IN KSHV INFECTED DMVEC CELLS AND<br />
KAPOSI’S SARCOMA: IMPLICATIONS FOR TUMORIGENESIS<br />
Donald J. Alcendor 1 Wen Qui Zhu 1 Prashant Desai 2 <strong>and</strong> Gary S. Hayward 2<br />
1 Meharry <strong>Medical</strong> <strong>College</strong>, School <strong>of</strong> Medicine, Center for AIDS Health Disparities<br />
Research <strong>and</strong> Department <strong>of</strong> Microbial Pathogenesis <strong>and</strong> Immune Response, 1005 Dr.<br />
D.B. Todd Jr. Blvd., Hubbard Hospital, Rm. 5025, Nashville, Tennessee, 37208-3599,<br />
USA, 2 Department <strong>of</strong> Viral Oncology <strong>and</strong> Pharmacology, Molecular Virology Laboratories,<br />
Sidney-Kimmel Cancer Research Center, Johns Hopkins <strong>University</strong> School <strong>of</strong> Medicine,<br />
Baltimore, Maryl<strong>and</strong> 21231-1000 USA<br />
Abstract<br />
The Galectins are a family <strong>of</strong> proteins that share an affinity for b-galactoside containing<br />
glycoconjugates. Galectin-3 has been implicated in tumor progression <strong>and</strong> metastasis.<br />
Down regulation <strong>of</strong> Galectin-3 is associated with malignancy in prostate, ovarian <strong>and</strong><br />
breast cancer. Kaposi’s sarcoma (KS) is characterized as an angioproliferative tumor <strong>of</strong><br />
vascular endothelial cells <strong>and</strong> produces rare B cell lymphoproliferative diseases in the<br />
form <strong>of</strong> primary effusion lymphomas (PEL) <strong>and</strong> some forms <strong>of</strong> Multicentric Castleman’s<br />
Disease (MDC). We have observed suppression <strong>of</strong> galectin-3 expression in KSHV infected<br />
dermal microvascular endothelial cells (DMVEC) <strong>and</strong> KS tumor tissue. Here we<br />
demonstrate that galectin-3 protein expression is downregulated 20-fold in KSHV<br />
infected DMVEC cells by immunoblot analysis. In infected DMVEC, we show absence <strong>of</strong><br />
galectin-3 staining by dual labeled immun<strong>of</strong>luorescence in latency associated nuclear<br />
antigen (LANA) positive spindle cells. There is also transcriptional suppression <strong>of</strong><br />
Galectin-3 message in KSHV infected DMVEC cells as observed by RT-PCR. Furthermore<br />
we find reduced levels <strong>of</strong> galectin-3 expression in LANA positive spindle cell regions in<br />
archival KS tissue by dual labeled immunohistochemistry. Transfection studies reveal<br />
KSHV vFLIP is likely the viral gene that targets galectin-3 downregulation in HeLa cells.<br />
Finally, in uninduced PEL cells lines galectin-3 expression levels vary with levels <strong>of</strong> KSHV<br />
replication. The search for novel host cell factors that may contribute to the overall<br />
pathogenesis <strong>of</strong> KS is essential for early detection <strong>of</strong> KS <strong>and</strong> development <strong>of</strong> innovative<br />
therapies for treatment.<br />
Presenting author Email: dalcendor@mmc.edu<br />
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