Soluble intercellular and vascular cell adhesion molecules-1 in lymphoid neoplasms: A clinical and prognostic study of Hodgkin's disease, non-Hodgkin's lymphomas and chronic B-lymphocytic leukaemia
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
The interaction of soluble adhesion molecules with adhesion ligands expressed by immunological cells interfere with the cell-cell adhesion essential for the signal transductions that initiate immunological responses. Preliminary data suggest that soluble adhesion molecules also promote angiogenesis. Thus dysregulated production of soluble adhesion molecules may emerge as participants of disturbed immuno- surveillance, lymphocyte trafficking and dissemination of cancer cells. Vascular cell adhesion molecule-l (VCAM-1) and intercellular adhesion molecule-l (ICAM-1) are inducible and/or upregulated by cytokines in different cells types such as endothelial cells, follicular dendritic cells, and stromal cells. Lymphoid neoplasms, representing malignant counterparts of immunological cells, are characterised by heterogeneous histopathologies and clinical manifestations.
Serum levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were elevated in Hodgkin's disease (HD) and chronic B-lymphocytic leukaemia (B-CLL), while only sICAM-1 was elevated in non-Hodgkin's lymphomas (NHL). Serum levels of sICAM-1 and sVCAM-1 correlated with tumour burden and other known prognostic markers. sICAM-1 was an independent prognostic variable in HD and B-CLL. sVCAM-1 was an independent prognostic variable in HD. The discriminative power of serum levels of sVCAM-1 in smouldering and non-smouldering B-CLL could prove clinically valuable.
Both ICAM-1 and VCAM-1 were overexpressed by vascular endothelium and stroma in biopsies of HD, B-CLL and NHL. No correlation between tissue expression of the adhesion molecules and the serum levels of sICAM-1 and sVCAM-1 appeared. VCAM-1 was expressed by two of seven HD cell lines, and sVCAM-1 was detectable in supernatants from these two cell lines. ICAM-1 was expressed by all I-ID cell lines and detectable in supernatants. In the majority of B-CLL and NHL cultures, ICAM-1 expression was upregulated by tumour cells, resulting in detectable sICAM-1 in supernatants.
In conclusion, serum levels of both sICAM-1 and sVCAM-1 had prognostic powers equalling or surpassing known prognostic markers in lymphoid neoplasms. The functional consequences of dysregulated serum levels of sICAM-1 and sVCAM-1 in lymphoid neoplasms is at present largely unknown.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 72 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 746
Oncology, Hodgkin's disease, non-Hodgkin's lymphomas, chronic lymphocytic leukaemia, sICAM-1, sVCAM-1, prognostic markers, VCAM-1, ICAM-1, Hodgkin cell lines
Cancer and Oncology
Research subject Clinical Immunology
IdentifiersURN: urn:nbn:se:uu:diva-152ISBN: 91-554-4163-7OAI: oai:DiVA.org:uu-152DiVA: diva2:161103
1998-05-22, Skoogsalen, ingång 78, Akademiska sjukhuset, Uppsala, Uppsala, 09:15