Study of Human Tumour Draining Lymph Node Homing Receptors in Breast Cancer Patients

Park, Bae-Keun (1994) Study of Human Tumour Draining Lymph Node Homing Receptors in Breast Cancer Patients. PhD thesis, University of Glasgow.

Abstract

The cell surface molecule LEU-8 has been reported to identify the human homologue of the MEL-14 lymph node homing receptor by sequence comparison of the two antigens (Camerini et al., 1989). However, it has never been directly tested for its ability to specifically detect lymphocytes which home to human lymph nodes. This study was designed to generate monoclonal antibodies against the nodal lymphocytes in order to identify marker unique to the node, and to compare this with the homing function suggested for the LEU-8 marker. At the same time, LEU-8 was tested for a homing function in humans by comparison of its relative expression in lymph node and peripheral blood of breast cancer patients using two-colour flow cytometry. This work also set out to assess local immunological responses in the nodes and peripheral blood, and to analyse the expression in the nodes and its relationship to the expression pattern of the human lymphocyte homing receptor CD44. The antigens of human nodal lymphocytes identified by three monoclonal antibodies were not unique to the node, and no specific homing molecule was identified despite a logical strategy. The monoclonal antibodies produced were to B cell antigens that were unlikely to be MHC Class I or immunoglobulin. B cells were not quantitatively dominant in the human lymph node but were highly immunodominant. The data showed that CD3+ or CD 19+ cells did not express LEU-8 preferentially in the human lymph node, and indeed the latter showed a preference for location in the blood. LEU-8 was irrelevant to T lymphocyte homing and a negative indicator of B cell homing. Taken together, there was no functional evidence from this study that the LEU-8 cDNA homologous to mouse MEL-14 antigen does indeed encode a human lymph node homing receptor. In the local lymph nodes of breast cancer patients, the activation marker IL-2 receptor (Tac) was present on a higher proportion on CD4+ than CD8+ cells in two axillary lymph nodes (near and far from their draining tissue) and peripheral blood. In contrast, the percentage of CD8+ T cells bearing the activation marker HLA DR was higher than the percentage of HLA DR expressing CD4+ T cells in all cases. CD44 was preferentially located in the human lymph node, but did not show significance difference between lymph node and peripheral blood such that was difficult to deduce homing. This study suggest that CD44 might be a homing receptor in humans, but more data is required for statistical validity. More interestingly both CD44 and LEU-8 were present on primary and metastatic tumour cells, and may therefore have prognostic and diagnostic potential in primary and metastatic breast carcinomas.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Ailsa M Campbell
• Keywords: Biochemistry, Oncology
• Date of Award: 1994
• Depositing User: Enlighten Team
• Unique ID: glathesis:1994-76080
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 16:51
• Last Modified: 19 Nov 2019 16:51
• URI: https://theses.gla.ac.uk/id/eprint/76080