Purpose: Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), a specific molecular marker for lymph systems, has only one known ligand, hyaluronan (HA). Many studies have reported that HA, on the surface of tumor cells, is associated with the metastatic behavior of cancer cells. The interaction of LYVE-1 with HA may facilitate tumor cell attachment and enhance dissemination of tumor cells to lymph nodes. The aim of this study was to explore the biological function of LYVE-1 and to determine whether the interaction between LYVE-1 and HA was directly involved in the adhesion of tumor cells to lymphatic vessels.
Methods: COS-7 cells were transfected with cDNA encoding LYVE-1 and expressed LYVE-1 assembled exogenously added HA. A high HA-expressing breast cancer cell line, HS-578T, was chosen to be the upper layer of cells that adhered to a lower layer of COS-7LYVE-1(+), COS-7pegfp-N1, or COS-7 cells for the adhesion analyses. The mechanism of adhesion was investigated by an experiment in which the HA on the surface of HS-578T cells was digested by Streptomyces hyaluronidase before the HS-578T cells were allowed to adhere to COS-7LYVE-1(+) cells.
Results: Results showed that more adhesion was observed between HS-578T and COS-7LYVE-1(+) cells, while less adhesion was observed between HS-578T cells and either COS-7pegfp-N1 or COS-7 cells (p < 0.01). Decreased HA on the HS-578T cell surface could reduce the adhesion of HA-578T cells to COS-7LYVE-1(+) cells.suggesting that this adhesion might be mediated through HA.
Conclusion: Our results suggest that LYVE-1 allows the adhesion of tumor cells through the interaction of HA on the tumor cell membrane with LYVE-1