Gene Expression Profiling Associated with the Progression of Classic Kaposi's Sarcoma

European Journal of Inflammation

Original Article

R. Bergman¹  S.P. Nisticò²  N. Amariglio³  J. Jacob-Hirsch³  G. Rechavi³  J.G. Krueger⁴  S. Tintle⁴  A. Khatcherian⁴  A. Chiricozzi⁵  R. Sarid⁶  E. Guttman-Yassky⁷ 

[1] Department of Dermatology, Rambam Medical Center and the Technion, Haifa, Israel;Department of Dermatology, University of Rome Tor Vergata;Institute of Hematology and Sheba Cancer Research Center Tel Hashomer Sackler School of Medicine, Tel Aviv University, Israel;Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA;Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; Department of Dermatology, University of Rome Tor Vergata;Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel;Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; Department of Dermatology, Weill-Cornell Medical College, Cornell University, New York, USA; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA;

关键词: Kaposi's sarcoma (KS);    Kaposi sarcoma-associated herpes virus (KSHV);    lymphatic endothelium;    blood endothelium;   

DOI  :  10.1177/1721727X1201000313

 received in 2012-07-06, accepted in 2012-10-25,  发布年份 2012

来源: Sage Journals

【 摘 要 】

Although Kaposi's sarcoma (KS) gene expression profile is closer to lymphatic (LEC) rather than blood vascular endothelial cells (BEC), uncertainty still surrounds the cellular origin of KS. To follow KS progression from early to late (nodular) stage, and characterize the molecular fingerprinting associated with each stage, gene arrays were used to compare gene expression profile of 9 skin samples of classic KS (4 Early, 2 Mixed, and 3 Nodular CKS samples) to 4 normal samples. Results for selected genes were validated by Real-time (RT) PCR and immunohistochemistry. Genes regulating immune and defense responses, angiogenesis, apoptosis and proliferation were differentially expressed in different KS stages compared to normal skin. Hierarchical clustering separated normal skin from KS with a clear gradient from early to nodular KS lesions. The gene expression level of endothelium markers, metalloproteinases, angiogenic factors and chemokines, gradually increased from normal through all KS stages. The expression of LEC genes highly increased from early to nodular KS. In the initiation phase we noticed a higher expression of growth factors, as compared to progressive stages. LEC and BEC markers co-exist in “KS expression signature”, although the LEC signature prevailed. Our results also show a complex environment of inflammatory cells and chemokines during KS evolution. A pathogenic hypothesis where cellular hyperproliferation is driven by local expression of chemokines and growth factors without clonal expansion of cells is suggested.

【 授权许可】

Unknown   
© 2012 SAGE Publications