Suppressive effects on metastasis and tumor growth by the knockout of chemokine receptors in a canine cutaneous lymphoma model.

Abstract

Canine epitheliotropic cutaneous T-cell lymphoma (ECTCL) is a malignant neoplasm exhibiting various skin lesions. Metastasis to the lymph nodes and distant organs contributes to the poor prognosis of ECTCL; however, the underlying molecular mechanisms remain unclear. In the present study, the roles of chemokine receptors, such as CC chemokine receptor (CCR) 4 and CCR7, in the migration of tumor cells were examined using a canine cutaneous lymphoma model. Three mouse groups were prepared and xenografted with wild-type (WT), CCR4 knockout (KO), or CCR7KO canine ECTCL (EO-1) cells. The proportion of EO-1 cells in tissues and blood was significantly lower in the CCR4KO and CCR7KO groups than in the WT group. Only the iliac lymph node, a sentinel lymph node for the xenograft site, was enlarged with the infiltration of EO-1 cells in all groups. The size of the iliac lymph node was smaller in the KO groups than in the WT group. All mice developed a subcutaneous nodule at the xenograft site, which was smaller in the KO groups. In the cell proliferation assay, chemokine ligands stimulated an increase in EO-1 cells in the WT group, but not in the KO groups. These results suggest that CCR4 or CCR7 plays a vital role in the initial migration to sentinel lymph nodes and proliferation in a canine cutaneous lymphoma model.