Perri R T, Kay N E, McCarthy J, Vessella R L, Jacob H S, Furcht L T
Blood. 1982 Aug;60(2):430-5.
Control of neoplastic proliferation reflects in part monocyte/macrophage destruction of target cells--destruction that evidently requires cell-cell interaction. We herein show it to involve the natural plasma opsonin, fibronectin. With two cultured human tumor lines--Malme melanoma and CAK-I renal carcinoma cells--addition of fibronectin, purified to homogeneity, enhances macrophage-mediated cytotoxicity 2--4-fold (p less than 0.01). Both fresh human monocytes or the U-937-cultured macrophage line become more lethal to tumor cells with added fibronectin. The fibronectin-enhanced monocyte and U-937 tumoricidal activity occurred in a dose-dependent fashion. Specificity of fibronectin's action was validated by use of affinity-purified rabbit antifibronectin antibody, which completely abated its enhancement of tumoricidal activity. Enhancement of tumoricidal activity did not occur when monocytes or U-937 were exposed to fibronectin-coated plates. However, the addition of soluble fibronectin to fibronectin-coated plates was then capable of enhancing cytocidal activity. These studies demonstrate that human fibronectin is capable of increasing both fresh and cultured human monocyte tumor-directed cytotoxicity. Fibronectin appears to be a potentially important circulating molecule that may favorably influence human monocyte tumor cell cytotoxicity.
肿瘤增殖的控制部分反映为单核细胞/巨噬细胞对靶细胞的破坏——这种破坏显然需要细胞间相互作用。我们在此表明，这涉及天然血浆调理素纤维连接蛋白。对于两种培养的人类肿瘤细胞系——马尔默黑色素瘤细胞和CAK - I肾癌细胞——添加纯化至同质的纤维连接蛋白可使巨噬细胞介导的细胞毒性增强2至4倍（p小于0.01）。添加纤维连接蛋白后，新鲜的人类单核细胞或U - 937培养的巨噬细胞系对肿瘤细胞的杀伤力均增强。纤维连接蛋白增强的单核细胞和U - 937杀肿瘤活性呈剂量依赖性。使用亲和纯化的兔抗纤维连接蛋白抗体验证了纤维连接蛋白作用的特异性，该抗体完全消除了其对杀肿瘤活性的增强作用。当单核细胞或U - 937暴露于纤维连接蛋白包被的平板时，杀肿瘤活性并未增强。然而，向纤维连接蛋白包被的平板中添加可溶性纤维连接蛋白后能够增强细胞杀伤活性。这些研究表明，人类纤维连接蛋白能够增强新鲜的和培养的人类单核细胞对肿瘤的定向细胞毒性。纤维连接蛋白似乎是一种潜在的重要循环分子，可能对人类单核细胞对肿瘤细胞的细胞毒性产生有利影响。
