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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Pathogenesis Abstract 21
DOWNREGULATION OF GALECTIN-3 IN KSHV INFECTED DMVEC CELLS AND
KAPOSI’S SARCOMA: IMPLICATIONS FOR TUMORIGENESIS
Donald J. Alcendor 1 Wen Qui Zhu 1 Prashant Desai 2 and Gary S. Hayward 2
1 Meharry Medical College, School of Medicine, Center for AIDS Health Disparities
Research and Department of Microbial Pathogenesis and Immune Response, 1005 Dr.
D.B. Todd Jr. Blvd., Hubbard Hospital, Rm. 5025, Nashville, Tennessee, 37208-3599,
USA, 2 Department of Viral Oncology and Pharmacology, Molecular Virology Laboratories,
Sidney-Kimmel Cancer Research Center, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21231-1000 USA
Abstract
The Galectins are a family of proteins that share an affinity for b-galactoside containing
glycoconjugates. Galectin-3 has been implicated in tumor progression and metastasis.
Down regulation of Galectin-3 is associated with malignancy in prostate, ovarian and
breast cancer. Kaposi’s sarcoma (KS) is characterized as an angioproliferative tumor of
vascular endothelial cells and produces rare B cell lymphoproliferative diseases in the
form of primary effusion lymphomas (PEL) and some forms of Multicentric Castleman’s
Disease (MDC). We have observed suppression of galectin-3 expression in KSHV infected
dermal microvascular endothelial cells (DMVEC) and KS tumor tissue. Here we
demonstrate that galectin-3 protein expression is downregulated 20-fold in KSHV
infected DMVEC cells by immunoblot analysis. In infected DMVEC, we show absence of
galectin-3 staining by dual labeled immunofluorescence in latency associated nuclear
antigen (LANA) positive spindle cells. There is also transcriptional suppression of
Galectin-3 message in KSHV infected DMVEC cells as observed by RT-PCR. Furthermore
we find reduced levels of galectin-3 expression in LANA positive spindle cell regions in
archival KS tissue by dual labeled immunohistochemistry. Transfection studies reveal
KSHV vFLIP is likely the viral gene that targets galectin-3 downregulation in HeLa cells.
Finally, in uninduced PEL cells lines galectin-3 expression levels vary with levels of KSHV
replication. The search for novel host cell factors that may contribute to the overall
pathogenesis of KS is essential for early detection of KS and development of innovative
therapies for treatment.
Presenting author Email: dalcendor@mmc.edu
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