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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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NEOPLASIA

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

Yue Ma1,2, Lydia Visser1, Han Roelofsen2, Marcel de Vries1, Arjan Diepstra1, Gustaaf van Imhoff3, Tineke van der Wal3, Marjan Luinge1, Gloria Alvarez-Llamas2, Hans Vos1, Sibrand Poppema1, Roel Vonk2, and Anke van den Berg1

1 Department of Pathology & Laboratory Medicine, 2 Centre for Medical Biomics, and 3 Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphoma (HL) secrete factors that interact with 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 4 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 secreted proteins revealed 37 proteins involved in immune response. Sixteen of the 37 proteins (ie, ALCAM, Cathepsin C, Cathepsin S, CD100, CD150, CD26, CD44, CD63, CD71, Fractal-kine, 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 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 with healthy controls. Proteomics analyses of HL cell line supernatant allowed 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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