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Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
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2001 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 114, no 3, 616-623 p.Article in journal (Refereed) Published
Abstract [en]

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Place, publisher, year, edition, pages
2001. Vol. 114, no 3, 616-623 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-92248DOI: 10.1046/j.1365-2141.2001.02977.xPubMedID: 11552987OAI: oai:DiVA.org:uu-92248DiVA: diva2:165255
Available from: 2004-10-08 Created: 2004-10-08 Last updated: 2010-11-22Bibliographically approved
In thesis
1. Mast cells in Hodgkin lymphoma: or 'What's a nice cell like you doing in a tumour like this?'
Open this publication in new window or tab >>Mast cells in Hodgkin lymphoma: or 'What's a nice cell like you doing in a tumour like this?'
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mast cell (MC) accumulation around tumours is an old observation gaining new relevance due to the multifaceted nature of MCs and their many roles in immunity, beyond allergy. Knowledge about tumour specific recruitment of, and interactions with, MCs is needed to unravel the function of their presence.

This study investigates the participation of mast cells in the tumourigenesis of Hodgkin lymphoma (HL), a tumour with many inflammatory features. We report that MC recruitment into HL lymphomatous tissue is possibly due to the production of CCL5/RANTES by malignant Hodgkin and Reed-Sternberg (HRS) cells. In addition, increased levels of IL-9, a cytokine implicated in mast cell heterogeneity and as an autocrine growth factor for HRS cells, were found in HL patient sera and correlate with negative prognostic factors. The ubiquitous expression of CD30 by HRS cells has been implicated in HL tumour development. In HL tissue MCs were found to be the predominant CD30 ligand (CD30L) expressing cells, and through CD30L/CD30 engagement they induced a proliferative response in HRS cells. This interaction proved to be bi-directional as it induced a degranulation-independent de novo synthesis of a specific set of chemokines in MCs, including IL-8. This novel trigger of MC activation is suggested to be of importance also in atopic dermatitis (AD) and psoriasis since increased numbers of CD30L and IL-8 positive MCs were detected along with increased expression of CD30.

Data presented in this study supports a specific recruitment of MCs into HL tumours and co-operative interactions between HRS cells and MCs. Our identification of reversed signalling via CD30L as a novel MC trigger provides a mechanism behind leukocyte infiltration and chronic development in diseases associated with CD30 and MCs, such as HL, AD and psoriasis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 63 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1380
Pathology, Hodgkin lymphoma, mast cells, CD30, CD30L, IL-9, CCL5, atopic dermatitis, psoriasis, IL-8, Patologi
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-4620 (URN)91-554-6062-3 (ISBN)
Public defence
2004-10-29, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 09:15
Available from: 2004-10-08 Created: 2004-10-08Bibliographically approved

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