The Interaction between LYVE-1 with Hyaluronan on the Cell Surface May Play a Role in the Diversity of Adhesion to Cancer Cells

Yan Du,Hua Liu,Wenjuan Wang,Feng Gao,Muqing Zhou,Jiajie Hu,Lian Cui,Cuixia Yang,Yiwen Liu,Yiqing He,Nikos K Karamanos

doi:10.1371/journal.pone.0063463

Abstract

Hyaluronan (HA), a simple disaccharide unit, can polymerize and is considered a primary component of the extracellular matrix, which has a wide range of biological functions. In recent years, HA was found on the surface of tumor cells. According to previous reports, differing HA content on the cell surface of tumor cells is closely related to lymph node metastases, but the mechanisms mediating this process remained unclear. This research intended to study the surface content of HA on tumor cells and analyze cell adhesive changes caused by the interaction between HA and its lymphatic endothelial receptor (LYVE-1). We screened and observed high HA content on HS-578T breast cells and low HA content on MCF-7 breast cells through particle exclusion, immunofluorescence and flow cytometry experiments. The expression of LYVE-1, the lymph-vessel specific HA receptor, was consistent with our previous report and enhanced the adhesion of HAhigh-HS-578T cells to COS-7LYVE-1(+) through HA in cell static adhesion and dynamic parallel plate flow chamber experiments. MCF-7 breast cells contain little HA on the surface; however, our results showed little adhesion difference between MCF-7 cells and COS-7LYVE-1(+) and COS-7LYVE-1(−) cells. Similar results were observed concerning the adhesion of HS-578T cells or MCF-7 cells to SVEC4-10 cells. Furthermore, we observed for the first time that the cell surface HA content of high transfer tumor cells was rich, and we visualized the cross-linking of HA cable structures, which may activate LYVE-1 on lymphatic endothelial cells, promoting tumor adhesion. In summary, high-low cell surface HA content of tumor cells through the interaction with LYVE-1 leads to adhesion differences.

Highlights

Invasion and metastasis are the most important biological characteristics of malignant tumors
Our results showed that MDA-MB-435S, MDA-MB-468, MCF-7, and SK-BR-3 cells, which have a low capacity for HA production, were not excluded from fixed erythrocytes (Fig. 1A e, g, I, k), and almost no change was observed after adding hyaluronidase (Fig. 1A f, h, j, l)
These findings suggest that HA on the tumor surface may participate in breast tumor metastasis by influencing binding with LYVE-1 on lymph vessel endothelial cells

Summary

Introduction

Invasion and metastasis are the most important biological characteristics of malignant tumors. Tumor cell adhesion plays an important role in tumor invasion and metastasis, including the connection between tumor cells themselves and between tumor cells with other cell types. The transfer of tumor cells involves adhesion and separation (adhesion depolymerization). During the middle stage of invasion, tumor cells that were transferred into the circulation system adhere to vascular endothelial cells and the extracellular matrix. This process involves many adhesion factors and various other factors that promote or separate adhesion such as cell adhesion molecules (CD44, cadherin). This study primarily discusses problems in adhesion involving tumor cells and lymph endothelial cells

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Conclusion