Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte-colon carcinoma cell adhesive interactions

The ability of tumor cells to metastasize hematogenously is regulated by th eir interactions with polymorphonuclear leukocytes (PMNs). However, the mec hanisms mediating PMN binding to tumor cells under physiological shear forc es remain largely unknown. This study was designed to characterize the mole cular interactions between PMNs and tumor cells as a function of the dynami c shear environment, using two human colon adenocarcinoma cell lines (LS174 T and HCT-8) as models. MIN and colon carcinoma cell suspensions, labeled w ith distinct fluorophores, were sheared in a cone-and-plate rheometer in th e presence of the PMN activator fMLP. The size distribution and cellular co mposition of formed aggregates were determined by flow cytometry. PMN bindi ng to LS174T cells was maximal at 100 s(-1) and decreased with increasing s hear. At low shear (100 s(-1)) PMN CD11b alone mediates PMN-LS174T heteroag gregation. However, L-selectin, CD11a, and CD11b are all required for PMN b inding to sialyl Lewis-bearing LS174T cells at high shear (800 s(-1)). In c ontrast, sialyl Lewis -low HCT-8 cells fail to aggregate with PMNs at high shear conditions, despite extensive adhesive interactions at low shear. Tak en together, our data suggest that PMN L-selectin initiates LS174T cell tet hering at high shear by binding to sialylated moieties on the carcinoma cel l surface, whereas the subsequent involvement of CD11a and CD11b converts t hese transient tethers into stable adhesion. This study demonstrates that t he shear environment of the vasculature modulates the dynamics and molecula r constituents mediating PMN-tumor cell adhesion.