title: L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions.
abstract: Cell migration in blood flow is mediated by engagement of specialized adhesion molecules that function under hemodynamic shear conditions, and many of the effectors of these adhesive interactions, such as the selectins and their ligands, are well defined. However, in contrast, our knowledge of the adhesion molecules operant under lymphatic flow conditions is incomplete. Among human malignancies, head and neck squamous cell cancer displays a marked predilection for locoregional lymph node metastasis. Based on this distinct tropism, we hypothesized that these cells express adhesion molecules that promote their binding to lymphoid tissue under lymphatic fluid shear stress. Accordingly, we investigated adhesive interactions between these and other cancer cells and the principal resident cells of lymphoid organs, lymphocytes. Parallel plate flow chamber studies under defined shear conditions, together with biochemical analyses, showed that human head and neck squamous cell cancer cells express heretofore unrecognized L-selectin ligand(s) that mediate binding to lymphocyte L-selectin at conspicuously low shear stress levels of 0.07-0.08 dynes/cm(2), consistent with lymphatic flow. The binding of head and neck squamous cancer cells to L-selectin displays canonical biochemical features, such as requirements for sialylation, sulfation, and N-glycosylation, but displays a novel operational shear threshold differing from all other L-selectin ligands, including those expressed on colon cancer and leukemic cells (e.g. HCELL). These data define a novel class of L-selectin ligands and expand the scope of function for L-selectin within circulatory systems to now include a novel activity within shear stresses characteristic of lymphatic flow.
authors.affiliation: Department of Otolaryngology and the Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Vicente A
authors.initials: VA
authors.lastname: Resto
authors.forename: Monica M
authors.initials: MM
authors.lastname: Burdick
authors.forename: Nilesh M
authors.initials: NM
authors.lastname: Dagia
authors.forename: Susan D
authors.initials: SD
authors.lastname: McCammon
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fennewald
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
mesh_terms: D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008196:Lymph / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D033081:Shear Strength
chemical_list: D008024:Ligands; D009363:Neoplasm Proteins; D019041:L-Selectin