KSHV downregulation of galectin-3 in Kaposi's sarcoma

Donald J. Alcendor, Susan M. Knobel, Prashant Desai, Wen Q. Zhu, Hollie E. Vigil, Gary S. Hayward

Research output: Contribution to journalArticle

Abstract

Galectins are a family of proteins that share an affinity for beta-galactoside containing glycoconjugates. In prostate, ovarian and breast cancer, downregulation of galectin-3 is associated with malignancy and tumor progression. 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 and some forms of multicentric Castleman's disease. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS. We found reduced levels of galectin-3 expression in a significant fraction of latency-associated nuclear antigen (LANA)-positive spindle cell regions in human archival KS tissue and as measured in KS tissue microarrays. Here we demonstrate that galectin-3 protein expression is downregulated 10-fold in 10-day KSHV-infected dermal microvascular endothelial cells (DMVEC) accompanied by downregulation of message. There is loss of galectin-3 staining in KSHV-infected DMVEC by dual labeled immunohistochemistry in LANA-positive spindle cells. We observed a consistent downregulation of galectin-3 by time-course transcriptional analysis. Of the galectins assayed, only galectin-1 was also downregulated in KSHVinfected DMVEC. We examined 86 KS tumors; 19 were LANA positive (22%) and 67 LANA negative (78%). All 86 tumors were found to be galectin-3 positive; 11 of 19 showed reduced expression of galectin-3 in LANA-positive spindle cell regions. Our data suggest that KSHV vFLIP and LANA are the viral genes targeting galectin-3 downregulation. The contribution of host factors to the pathogenesis of KS is essential for early detection and development of innovative therapies for treatment.

Original languageEnglish (US)
Article numbercwp204
Pages (from-to)521-532
Number of pages12
JournalGlycobiology
Volume20
Issue number5
DOIs
StatePublished - Dec 29 2009

Keywords

  • Endothelial cells
  • Galectin-3
  • Immunohistochemistry
  • Kaposi's sarcoma
  • Transcriptional suppression

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Alcendor, D. J., Knobel, S. M., Desai, P., Zhu, W. Q., Vigil, H. E., & Hayward, G. S. (2009). KSHV downregulation of galectin-3 in Kaposi's sarcoma. Glycobiology, 20(5), 521-532. [cwp204]. https://doi.org/10.1093/glycob/cwp204