TY - JOUR
T1 - In vitro exposure to paclitaxel modulates integrin expression by human T lymphocytes and inhibits T cell adhesion to breast carcinoma cells
AU - Bhan, Vineet
AU - Mader, Jamie S.
AU - Hoskin, David W.
PY - 2004/4
Y1 - 2004/4
N2 - Paclitaxel (Taxol) is a drug that is commonly used in the treatment of metastatic breast cancer. In this study, we investigated the effect of prior exposure to submaximal cytotoxic concentrations (EC25 and EC 50) of paclitaxel on the subsequent ability of human Jurkat T lymphocytes to adhere to monolayers of MDA-MB-435 human breast carcinoma cells. Jurkat T cells that survived culture for 24 h in the presence of paclitaxel (0.1 or 3 μg/ml) exhibited a diminished ability to adhere to MDA-MB-435 breast cancer cell monolayers. Flow cytometric analysis of paclitaxel-treated Jurkat T cells revealed reduced surface expression of αL, α4, α5, and β7 integrins, but normal β1 integrin expression. These data suggest that paclitaxel interferes with the expression of αLβ 2 (LFA-1), α4β1 (VLA-4), α5β1 (VLA-5), and α4β 7 (LPAM-1) adhesion molecules by surviving T cells. Blocking experiments with antibodies against αL, β4, α5, β1 and β7 integrins revealed that adhesion of Jurkat T cells to MDA-MB-435 breast cancer cell monolayers was dependent upon αL, α4, and β7 but not α5or β1 integrins. We conclude that prior exposure to paclitaxel caused a reduction in Jurkat T cell adhesion to MDA-MB-435 breast carcinoma cells by preventing optimal αLβ2 and α4β7 interactions with their corresponding ligands on tumor cells. A similar effect by paclitaxel on T lymphocytes of breast cancer patients may compromise cell-mediated anti-tumor immune responses.
AB - Paclitaxel (Taxol) is a drug that is commonly used in the treatment of metastatic breast cancer. In this study, we investigated the effect of prior exposure to submaximal cytotoxic concentrations (EC25 and EC 50) of paclitaxel on the subsequent ability of human Jurkat T lymphocytes to adhere to monolayers of MDA-MB-435 human breast carcinoma cells. Jurkat T cells that survived culture for 24 h in the presence of paclitaxel (0.1 or 3 μg/ml) exhibited a diminished ability to adhere to MDA-MB-435 breast cancer cell monolayers. Flow cytometric analysis of paclitaxel-treated Jurkat T cells revealed reduced surface expression of αL, α4, α5, and β7 integrins, but normal β1 integrin expression. These data suggest that paclitaxel interferes with the expression of αLβ 2 (LFA-1), α4β1 (VLA-4), α5β1 (VLA-5), and α4β 7 (LPAM-1) adhesion molecules by surviving T cells. Blocking experiments with antibodies against αL, β4, α5, β1 and β7 integrins revealed that adhesion of Jurkat T cells to MDA-MB-435 breast cancer cell monolayers was dependent upon αL, α4, and β7 but not α5or β1 integrins. We conclude that prior exposure to paclitaxel caused a reduction in Jurkat T cell adhesion to MDA-MB-435 breast carcinoma cells by preventing optimal αLβ2 and α4β7 interactions with their corresponding ligands on tumor cells. A similar effect by paclitaxel on T lymphocytes of breast cancer patients may compromise cell-mediated anti-tumor immune responses.
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U2 - 10.3892/or.11.4.893
DO - 10.3892/or.11.4.893
M3 - Article
C2 - 15010891
AN - SCOPUS:16544395804
SN - 1021-335X
VL - 11
SP - 893
EP - 897
JO - Oncology Reports
JF - Oncology Reports
IS - 4
ER -