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Mast cells in Hodgkin lymphoma: or 'What's a nice cell like you doing in a tumour like this?'
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
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. , p. 63
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1380
Keywords [en]
Pathology, Hodgkin lymphoma, mast cells, CD30, CD30L, IL-9, CCL5, atopic dermatitis, psoriasis, IL-8
Keywords [sv]
Patologi
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-4620ISBN: 91-554-6062-3 (print)OAI: oai:DiVA.org:uu-4620DiVA, id: diva2:165259
Public defence
2004-10-29, Rudbecksalen, Rudbecklaboratoriet, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-10-08 Created: 2004-10-08 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
Open this publication in new window or tab >>Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
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2001 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 114, no 3, p. 616-623Article 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92248 (URN)10.1046/j.1365-2141.2001.02977.x (DOI)11552987 (PubMedID)
Available from: 2004-10-08 Created: 2004-10-08 Last updated: 2017-12-14Bibliographically approved
2. Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue
Open this publication in new window or tab >>Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue
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2003 In: International Journal of Cancer, ISSN 1097-0215, Vol. 107, no 2, p. 197-201Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92249 (URN)
Available from: 2004-10-08 Created: 2004-10-08Bibliographically approved
3. Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma
Open this publication in new window or tab >>Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma
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2003 In: Leukemia, ISSN 0887-6924, Vol. 17, no 12, p. 2513-2516Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92250 (URN)
Available from: 2004-10-08 Created: 2004-10-08Bibliographically approved
4. Activation of mast cells through CD30 ligand (CD30L) induces degranulation-independent chemokine production and mast cell CD30L expression is up-regulated in cutaneous inflammatory diseases
Open this publication in new window or tab >>Activation of mast cells through CD30 ligand (CD30L) induces degranulation-independent chemokine production and mast cell CD30L expression is up-regulated in cutaneous inflammatory diseases
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Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-92251 (URN)
Available from: 2004-10-08 Created: 2004-10-08Bibliographically approved

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