Kowitz A, Kadmon G, Verschueren H, Remels L, De Baetselier P, Hubbe M, Schachner M, Schirrmacher V, Altevogt P
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Clin Exp Metastasis. 1993 Sep;11(5):419-29. doi: 10.1007/BF00132985.
The cell adhesion molecule (CAM) L1 is involved in homotypic and heterotypic adhesion between neural cells. It has recently also been identified on leucocytes. We have investigated the expression of L1 on hematopoietic tumor cell lines and found that several tumors including the ESb-MP lymphoma are positive for L1. A potential role for L1 in spontaneous metastasis formation was examined using these cells. From wild-type (wt) L1high lymphoma cells we selected by a fluorescence-activated cell sorter (FACS) stable L1low expression variants. Syngeneic DBA/2 mice injected subcutaneously with L1low clones showed faster primary tumor growth, developed visceral metastases significantly faster and died earlier than animals carrying L1high wt cells. L1 high revertants from the L1low variants showed again a reduced metastatic capacity and a malignancy similar to the wt cells. Expression of L1 on the tumor variants and revertants correlated directly with their homotypic aggregation behaviour in vitro. L1 expression correlated negatively with metastatic capacity. These results suggest that L1 molecules may contribute to the overall malignant potential of the lymphoma cells, presumably by interfering with cell-cell interactions critical for tumor growth and dissemination.
细胞黏附分子(CAM)L1参与神经细胞之间的同型和异型黏附。最近在白细胞上也发现了它。我们研究了造血肿瘤细胞系上L1的表达,发现包括ESb-MP淋巴瘤在内的几种肿瘤L1呈阳性。利用这些细胞研究了L1在自发转移形成中的潜在作用。通过荧光激活细胞分选仪(FACS)从野生型(wt)L1高表达淋巴瘤细胞中筛选出稳定的L1低表达变体。皮下注射L1低克隆的同基因DBA/2小鼠比携带L1高野生型细胞的动物原发性肿瘤生长更快,内脏转移明显更快,死亡更早。L1低变体的L1高回复株再次显示出转移能力降低,恶性程度与野生型细胞相似。肿瘤变体和回复株上L1的表达与它们在体外的同型聚集行为直接相关。L1表达与转移能力呈负相关。这些结果表明,L1分子可能对淋巴瘤细胞的整体恶性潜能有贡献,大概是通过干扰对肿瘤生长和扩散至关重要的细胞间相互作用。