The in vitro acquisition of CD11a by gastric cancer cells after contact with T cells via trogocytosis increases adhesion to endothelial cells.

Abstract

Background: Recent studies reveal that during trogocytosis plasma membranes are frequently transferred upon cell-to-cell contact, and that this phenomenon plays an important role in the modulation of anti-tumor immune response. However, the accompanying physiological roles in the tumor microenvironment are poorly understood.

Methods & results: Human gastric cancer cell line OCUM-1 was co-cultured with T cells whose plasma membrane was stained with PKH26. Flow-cytometric analysis revealed that OCUM-1 was positive for PKH26 at one hour and the positive rate increased over time. The acquisition of PKH26 was dependent on cell-to-cell contact and suppressed when T cells were fixed. OCUM-1 came to express various immunological synapse molecules after 10 hours of co-culture (positive rate, CD45:73.6±7.9%, CD3: 35.5±10.1%, CD4: 15.3±14.7%, CD8: 7.7±2.4%, CD11a: 8.1±4.3%, CD11b: 3.4±1.9%). We focused on CD11a which belongs to β2 integrins and aids immune cell adherence to endothelial cells. After co-culture with activated T cells (LAK), the expression level of CD11a on OCUM-1 was accelerated (with T cells: 19.1±13.4%, with LAK: 75.2±11.8%) and the adhesion rate on endothelial cells increased in a CD11a dependent manner (adhesion rate, single-culture: 2.0±0.64%, co-culture: 6.3±2.0%, co-culture (pre-treat with CD11a antibody): 2.3±1.4%, n=10, single-culture vs co-culture, p<0.0001; co-culture vs pre-treat with CD11a antibody, p<0.0001).

Conclusion: These results suggest that acquisition of CD11a from T cells by trogocytosis enables cancer cells to increase adhesive properties towards endothelial cells, which may result in intravenous metastasis promotion.