KSHV downregulation of galectin-3 in Kaposi's sarcoma
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Updated: Jun 17, 2026
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)
Published on: September 14, 2010
Donald J Alcendor1, Susan M Knobel, Prashant Desai
1Meharry Medical College, School of Medicine, Comprehensive Center for AIDS Health Disparities Research and the Department of Microbial Pathogenesis and Immune Response, Hubbard Hospital 1005 Dr. D.B. Todd Jr. Blvd., Nashville, TN 37208-3599, USA. dalcendor@mmc.edu
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 KSHV-infected 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.
Insights
Kaposi
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- Galectins, particularly galectin-3, are implicated in various cancers, with downregulation associated with malignancy.
- Kaposi's sarcoma (KS) is an angioproliferative tumor caused by Kaposi's sarcoma-associated herpesvirus (KSHV).
- KSHV infection leads to lymphoproliferative diseases, including primary effusion lymphomas and multicentric Castleman's disease.
Purpose of the Study:
- To investigate the expression levels of galectin-3 in Kaposi's sarcoma.
- To determine the effect of KSHV infection on galectin-3 expression in endothelial cells.
- To identify potential viral factors responsible for galectin-3 downregulation in KS.
Main Methods:
- Analysis of archival human KS tissue and KS tissue microarrays.
- Quantitative assessment of galectin-3 protein and mRNA levels in KSHV-infected dermal microvascular endothelial cells (DMVEC).
- Dual-labeled immunohistochemistry to visualize galectin-3 and latency-associated nuclear antigen (LANA) in infected cells.
- Time-course transcriptional analysis to track galectin-3 expression changes.
Main Results:
- Reduced galectin-3 expression was observed in LANA-positive spindle cell regions of archival KS tissue.
- KSHV infection of DMVEC led to a significant 10-fold downregulation of galectin-3 protein and mRNA.
- Loss of galectin-3 staining was evident in LANA-positive KSHV-infected DMVEC.
- Galectin-1 was also found to be downregulated in KSHV-infected DMVEC.
- Reduced galectin-3 expression in LANA-positive regions was detected in 11 out of 19 (58%) KS tumors analyzed.
Conclusions:
- KSHV infection significantly downregulates galectin-3 expression in endothelial cells.
- Viral genes, specifically KSHV vFLIP and LANA, are suggested to target galectin-3 for downregulation.
- Understanding the role of host factors like galectin-3 in KS pathogenesis is crucial for early detection and novel therapeutic strategies.
