Nucleolin mediates the binding of cancer cells to L-selectin under conditions of lymphodynamic shear stress

Author:

Goldson Tovë M.123,Turner Kevin L.4,Huang Yinan56,Carlson Grady E.5,Caggiano Emily G.7,Oberhauser Andres F.289,Fennewald Susan M.123,Burdick Monica M.156ORCID,Resto Vicente A.123

Affiliation:

1. Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas

2. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas

3. University of Texas Medical Branch Cancer Center, Galveston, Texas

4. Department of Mechanical Engineering, Ohio University, Athens, Ohio

5. Department of Chemical and Biomolecular Engineering, Ohio University, Athens, Ohio

6. Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, Athens, Ohio

7. Biological Sciences Program, Honors Tutorial College, Ohio University, Athens, Ohio

8. Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas

9. Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas

Abstract

Head and neck squamous cell carcinoma (HNSCC) cells bind to lymphocytes via L-selectin in a shear-dependent manner. This interaction takes place exclusively under low-shear stress conditions, such as those found within the lymph node parenchyma. This represents a novel functional role for L-selectin-selectin ligand interactions. Our previous work has characterized as-of-yet unidentified L-selectin ligands expressed by HNSCC cells that are specifically active under conditions of low shear stress consistent with lymph flow. Using an affinity purification approach, we now show that nucleolin expressed on the surface of HNSCC cells is an active ligand for L-selectin. Parallel plate chamber flow-based experiments and atomic force microscopy (AFM) experiments show that nucleolin is the main functional ligand under these low-force conditions. Furthermore, AFM shows a clear relationship between work of deadhesion and physiological loading rates. Our results reveal nucleolin as the first major ligand reported for L-selectin that operates under low-shear stress conditions.

Funder

NIH-NCI

NIH

John Sealy Memorial Endowment Fund for Biomedical Research

Honors Tutorial College Apprenticeship Award

John J. Kopchick Translational Biomedical Sciences Award

Provost's Undergraduate Research Fund Award

Ohio University Baker Fund Award

1804 Fund Award

Howard Hughes Medical Institute Early Physician Scientist Award

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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