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2 integrin-ICAM-1 bindings between neutrophils and melanoma cells
1 Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, United States
2 National Microgravity Laboratory and Center for Biomechanics and Bioengineering, Institue of Mechanics, Chinese Academy of Sciences, Beijing, Beijing, China
3 Beijing, Beijing, China; National Microgravity Laboratory and Center for Biomechanics and Bioengineering, Institue of Mechanics, Chinese Academy of Sciences, Beijing, Beijing, China
* To whom correspondence should be addressed. E-mail: cxd23{at}psu.edu.
Cell adhesion, mediated by specific receptor-ligand interactions, plays an important role in biological processes such as tumor metastasis and inflammatory cascade. For example, interactions between
2 integrin (LFA-1 and/or Mac-1) on neutrophils (PMNs) and intercellular adhesion molecule (ICAM-1) on melanoma cells initiate the bindings of melanoma cells to PMNs within the tumor microenvironment in blood flow, which in turn activate PMN-melanoma cell aggregation in the near vascular endothelium (EC) region, therefore enhancing subsequent extravasation of melanoma cells in the microcirculations. Kinetics of integrin-ligand bindings in a shear flow is the determinant to such a process, which has not been well understood. In this study, interactions of PMNs to WM9 melanoma cells were investigated to quantify the kinetics of
2 integrin-ICAM-1 bindings using a cone-plate viscometer that generates a linear shear flow combined with a two-color flow cytometry technique. Aggregation fractions exhibited a transition phase where it firstly increased and then decreased with shear durations generated by the cone-plate viscometer. It was also inversely correlated with the shear rate. A previously-developed probabilistic model was modified to predict the time dependence of aggregation fractions at different shear rates and medium viscosities. Kinetic parameters of
2 integrin-ICAM-1 bindings were obtained by individual or global fittings, which were comparable to respectively published values. These findings provide a new insight into quantitative understandings to the biophysical bases of leukocyte-tumor cell interactions mediated by specific receptor-ligand interactions under shear flow conditions.
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