Lymphokine-activated killer cell susceptibility and adhesion molecule expression of multidrug resistant breast carcinoma |
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Authors: | Burhan Savas Pauline E Kerr Hugh F Pross |
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Institution: | (1) Dept. of Oncology, Akdeniz University, Antalya, Turkiye;(2) Dept. of Microbiology and Immunology, Queen's University, Kingston, Canada |
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Abstract: | Reports showing susceptibility of multidrug resistant (MDR) cancer cells to immune effectors, together with P-glycoprotein
(P-gp) expression in immune effector subsets, including immature natural killer (NK) cells, and some activated T cells, suggest
P-gp or some changes associated with it, have implications in immune-mediated mechanisms. A series of experiments were done
to determine the nature of alterations associated with susceptibility to immune effector cells of MDR tumor cells. A cell
line isolated from the malignant pleural effusion of a breast cancer patient was transfected with human and murine MDR1 genes,
and four variants with different levels of MDR were obtained. Lymphokine-activated killer (LAK) activity was measured by a
51Chromium release, and conjugate formation assays. MDR1 transfectant P-gp+ breast carcinoma lines had increased LAK susceptibility compared to their parent line. Some part of the increased LAK susceptibility
of drug-resistant cell lines was at the binding/recognition level as shown by conjugate formation assays. This suggests that
differences may exist between paired cell lines with respect to the expression of cell adhesion molecules (CAMs). Monoclonal
antibodies (mAbs) to CAMs and flow cytometry were used to quantitate these antigens. The CAMs studied were those previously
found to be upregulated by stimulating NK cells with (interleukin-2) IL-2; ICAM-1 (CD54), LFA-3 (CD58), N-CAM (CD56), and
the β chain of LFA-1 (CD18). Although no differences in these CAMs were found between the breast carcinoma line and its MDR1-transfected
variants, the target susceptibility results given above suggest that IL-2 treatment could be effective in combination with
current protocols using chemotherapeutics, monoclonal antibodies (mAbs) and stem cell transplantation. |
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