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 Blood, 15 February 2008, Vol. 111, No. 4, pp. 2339-2346.
Prepublished online as a Blood First Edition Paper on December 10, 2007; DOI 10.1182/blood-2007-09-112128.

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Submitted September 14, 2007
Accepted November 28, 2007

Proteomics analysis of Hodgkin lymphoma: Identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

Yue Ma, Lydia Visser, Han Roelofsen, Marcel de Vries, Arjan Diepstra, Gustaaf van Imhoff, Tineke van der Wal, Marjan Luinge, Gloria Alvarez-Llamas, Hans Vos, Sibrand Poppema, Roel Vonk, and Anke van den Berg*

Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Centre for Medical Biomics, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands

* Corresponding author; email: a.van.den.berg{at}path.umcg.nl.

HRS cells in HL secrete factors that interact with the inflammatory background cells and may serve as biomarkers for disease activity. To detect new proteins related to pathogenesis, we analyzed the secretome of HRS cells. Proteins in cell culture supernatant of four HL cell lines were identified using 1DGE followed by in-gel trypsin digestion and LC-MS/MS. In total 1290 proteins, including 368 secreted proteins, were identified. Functional grouping of the secreted proteins revealed a total of 37 proteins involved in immune response. 16 of the 37 proteins, i.e. ALCAM, Cathepsin C, Cathepsin S, CD100, CD150, CD26, CD44, CD63, CD71, Fractalkine, IL1R2, IL25, IP-10, MIF, RANTES and TARC were validated in HL cell lines and patient material using immunohistochemistry and/or ELISA. Expression of all 16 proteins was confirmed in HL cell lines and 15 of these were also confirmed in HL tissues. Seven proteins (ALCAM, Cathepsin S, CD26, CD44, IL1R2, MIF and TARC) revealed significantly elevated levels in patient plasma compared to healthy controls. Proteomics analyses of HL cell line supernatant allowed the detection of new secreted proteins, which may add to our insights in the interaction between HRS cells and infiltrating lymphocytes and in some instances might serve as biomarkers.


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