Anti-gicerin Antibody Suppresses Early Pulmonary Metastatic Colonization of B16F10 Melanoma Cells.

BACKGROUND/AIM: Adhesion of circulating melanoma cells to the pulmonary vascular bed is a critical early step in hematogenous metastasis. Gicerin is an immunoglobulin superfamily cell adhesion molecule that can mediate homophilic cell-cell adhesion. We examined whether gicerin is expressed in B16F10 melanoma cells and pulmonary tissue and whether systemic anti-gicerin antibody suppresses experimental pulmonary colonization.

MATERIALS AND

METHODS

Gicerin expression was examined by immunofluorescence staining in cultured B16F10 cells, subcutaneous B16F10 tumors, pulmonary metastatic foci, and normal lung tissue, with matched rabbit pre-immune IgG controls processed in parallel. Histopathological features of subcutaneous and pulmonary lesions were evaluated by hematoxylin and eosin staining. Nude mice received a tail-vein injection of B16F10 cells followed immediately by intravenous administration of matched rabbit pre-immune IgG or rabbit polyclonal anti-gicerin IgG. Cell proliferation, adhesion to human umbilical vein endothelial cells (HUVECs), and wound-healing migration were assessed in vitro.

RESULTS

Gicerin immunoreactivity was detected in cultured B16F10 cells, subcutaneous tumors, pulmonary metastatic foci, and normal pulmonary structures, whereas matched rabbit pre-immune IgG controls showed no specific fluorescence, supporting staining specificity under the assay conditions. Tail-vein injection produced early pulmonary metastatic foci, and anti-gicerin IgG at 10 μg/mouse significantly reduced metastatic colonization compared with pre-immune IgG, whereas the 1 μg/mouse dose did not. Anti-gicerin IgG significantly inhibited B16F10 adhesion to HUVEC monolayers and significantly reduced cell migration without significantly affecting cell proliferation.

CONCLUSION

Gicerin contributes to early pulmonary colonization of B16F10 melanoma cells by supporting tumor-endothelial adhesion and tumor-cell migration. Gicerin blockade may represent a potential strategy for preventing hematogenous dissemination of melanoma.