Enforced expression of MCAM/MUC18 increases in vitro motility and invasiveness and in vivo metastasis of two mouse melanoma K1735 sublines in a syngeneic mouse model.

Human MCAM/MUC18 has been shown to increase metastasis of human melanoma cells in xenograft mouse systems. To be more relevant to understanding the progression of clinical melanoma and for designing better preclinical therapeutic trials, it is highly desirable to establish a syngeneic mouse model for studying the mechanisms of MCAM/MUC18-mediated tumorigenesis and metastasis of melanoma cells. To reach this goal, we transfected the mouse MCAM/MUC18 (moMCAM/MUC18) cDNA into two MCAM/MUC18-minus, low-metastatic mouse melanoma K1735 sublines, K1735-10 (tumor(-)/met(low)) and K1735-3 (tumor(+)/met(low)), and selected for G418-resistant clones, which expressed different levels of moMCAM/MUC18, and used for testing the effect of MCAM/MUC18 overexpression on their in vitro growth rate, motility, and invasiveness and in vivo subcutaneous tumor growth and pulmonary metastasis in syngeneic mice. Enforced expression of moMCAM/MUC18 did not significantly affect in vitro growth rate, but it increased the in vitro motility and invasiveness of clones derived from both sublines. Ectopic expression of moMCAM/MUC18 did not alter the nontumorigenicity of the K1735-10 clones per cells nor significantly affect the subcutaneous tumor growth of the K1735-3 clones per cells. The moMCAM/MUC18-expressing K1735-10 clones were able to establish only microscopic lung modules in 86% of the mice. In contrast, the moMCAM/MUC18-expressing K1735-3 clones could induce numerous large lung nodules (3-4 mm in diameter) in all the mice. We concluded that increased moMCAM/MUC18 expression in the two K1735 sublines minimally affected their tumorigenicity, but it augmented their in vitro motility and invasiveness and increased their pulmonary metastasis in the syngeneic C3H mice.