L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions

Vicente Resto, Monica M. Burdick, Nilesh M. Dagia, Susan D. McCammon, Susan M. Fennewald, Robert Sackstein

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15816-15824
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number23
DOIs
StatePublished - Jun 6 2008

Fingerprint

L-Selectin
Lymphocytes
Cell Communication
Cells
Fluids
Head and Neck Neoplasms
Ligands
Shear stress
Squamous Cell Neoplasms
Neoplasms
Adhesives
Molecules
Adhesion
Head
Glycosylation
Selectins
Tropism
Cell adhesion
Cell Adhesion Molecules
Hemodynamics

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Resto, V., Burdick, M. M., Dagia, N. M., McCammon, S. D., Fennewald, S. M., & Sackstein, R. (2008). L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions. Journal of Biological Chemistry, 283(23), 15816-15824. https://doi.org/10.1074/jbc.M708899200

L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions. / Resto, Vicente; Burdick, Monica M.; Dagia, Nilesh M.; McCammon, Susan D.; Fennewald, Susan M.; Sackstein, Robert.

In: Journal of Biological Chemistry, Vol. 283, No. 23, 06.06.2008, p. 15816-15824.

Research output: Contribution to journalArticle

Resto, V, Burdick, MM, Dagia, NM, McCammon, SD, Fennewald, SM & Sackstein, R 2008, 'L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions', Journal of Biological Chemistry, vol. 283, no. 23, pp. 15816-15824. https://doi.org/10.1074/jbc.M708899200
Resto, Vicente ; Burdick, Monica M. ; Dagia, Nilesh M. ; McCammon, Susan D. ; Fennewald, Susan M. ; Sackstein, Robert. / L-selectin-mediated lymphocyte-cancer cell interactions under low fluid shear conditions. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 23. pp. 15816-15824.
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