Faculty of Pharmacy, Keio University, Tokyo, Japan.
Oncol Rep. 2010 Feb;23(2):371-6.
The metastasis of malignant tumor cells from the primary tumor to distant sites in the body is a complex process. To identify genes that may be essential for metastasis, we established poorly metastatic mouse melanoma cells, namely Y925F-mutated FAK-transfected cells (Y925F cells), from the highly metastatic mouse melanoma cell line B16F10, and performed expression analyses. The expression of phospholipid protein 2 (PLP2) was markedly down-regulated in the Y925F cells. To elucidate the function of PLP2, we established melanoma cells overexpressing PLP2. We found that PLP2 enhanced proliferation, adhesion, invasion, and MMP-2 secretion in vitro, and tumor metastasis in vivo. These results suggest that PLP2 aids metastasis. Furthermore, we showed that PLP2 binds specifically to PI3K, thus activating Akt.
肿瘤细胞从原发性肿瘤转移到身体远处部位是一个复杂的过程。为了鉴定可能对转移至关重要的基因,我们从小鼠黑色素瘤高转移细胞系 B16F10 中建立了低转移性的小鼠黑色素瘤细胞,即 Y925F-FAK 转染细胞(Y925F 细胞),并进行了表达分析。在 Y925F 细胞中,磷脂蛋白 2(PLP2)的表达明显下调。为了阐明 PLP2 的功能,我们建立了过表达 PLP2 的黑色素瘤细胞。我们发现 PLP2 增强了体外的增殖、黏附、侵袭和 MMP-2 分泌,以及体内的肿瘤转移。这些结果表明 PLP2 有助于转移。此外,我们表明 PLP2 特异性地结合 PI3K,从而激活 Akt。