Gene expression profile of AIDS-related Kaposi's sarcoma.
BACKGROUND
Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome.


METHODS
In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results.


RESULTS
The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages.


CONCLUSIONS
The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages.
Cornelissen
Marion
M
Department of Human Retrovirology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. m.i.cornelisen@amc.uva.nl
van der Kuyl
Antoinette C
AC
van den Burg
Remco
R
Zorgdrager
Fokla
F
van Noesel
Carel J M
CJ
Goudsmit
Jaap
J
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000276:immunology; D037161:Galectins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D063267:Sialic Acid Binding Ig-like Lectin 1; D012867:Skin / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037161:Galectins; D007633:Keratins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D063267:Sialic Acid Binding Ig-like Lectin 1; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C571166:SIGLEC1 protein, human