Harimaya K, Tanaka K, Matsumoto Y, Sato H, Matsuda S, Iwamoto Y
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Clin Exp Metastasis. 2000;18(2):121-9. doi: 10.1023/a:1006791723233.
Osteosarcoma is the most frequent malignant bone tumor in children. It is highly invasive, however, the mechanisms behind osteosarcoma cell invasion are as yet still unknown. In the present study, treatment with TNFalpha enhanced the invasiveness of two human osteosarcoma cell lines, OST and MNNG. TNFalpha treatment also induced tumor cell motility, adhesion to laminin, the expression of matrix metalloproteinase 9 (MMP9), and the nuclear translocation of nuclear factor kappaB (NFkappaB) in the osteosarcoma cells. Moreover, antioxidants inhibited TNFalpha-induced osteosarcoma cell invasion, motility and NFkappaB nuclear translocation, but not adhesion to laminin or MMP9 expression. NFkappaB decoy, another NFkappaB inhibitor, also inhibited TNFalpha-induced osteosarcoma cell invasion and motility. Therefore, motility and NFkappaB activation were possibly related to TNFalpha-induced osteosarcoma cell invasion. However, adhesion to laminin or MMP did not demonstrate any correlation with TNFalpha-induced osteosarcoma cell invasion. Although NFkappaB is known to regulate TNFalpha-induced phenotypes, it may influence only motility and invasion, but not the MMP or laminin-mediated adhesion of these osteosarcoma cells.
骨肉瘤是儿童中最常见的恶性骨肿瘤。它具有高度侵袭性，然而，骨肉瘤细胞侵袭背后的机制仍不清楚。在本研究中，用肿瘤坏死因子α（TNFα）处理增强了两种人骨肉瘤细胞系OST和MNNG的侵袭性。TNFα处理还诱导了肿瘤细胞的运动性、对层粘连蛋白的粘附、基质金属蛋白酶9（MMP9）的表达以及骨肉瘤细胞中核因子κB（NFκB）的核转位。此外，抗氧化剂抑制了TNFα诱导的骨肉瘤细胞侵袭、运动性和NFκB核转位，但不抑制对层粘连蛋白的粘附或MMP9表达。另一种NFκB抑制剂NFκB诱饵也抑制了TNFα诱导的骨肉瘤细胞侵袭和运动性。因此，运动性和NFκB激活可能与TNFα诱导的骨肉瘤细胞侵袭有关。然而，对层粘连蛋白的粘附或MMP与TNFα诱导的骨肉瘤细胞侵袭没有任何相关性。尽管已知NFκB调节TNFα诱导的表型，但它可能仅影响运动性和侵袭，而不影响这些骨肉瘤细胞的MMP或层粘连蛋白介导的粘附。
