Saijo N, Ozaki A, Beppu Y, Takahashi K, Fujita J, Sasaki Y, Nomori H, Kimata M, Shimizu E, Hoshi A
J Cancer Res Clin Oncol. 1984;107(3):157-63. doi: 10.1007/BF01032600.
The mechanism of artificial and spontaneous metastases of tumor was analyzed in B16 melanoma cells and C57BL/6 mice by using anti-asialo GM1 antibody and anticancer agents. Single administrations of 500 micrograms anti-asialo GM1 antibody resulted in significantly decreased NK activity in spleen cells of C57BL/6 mice, lasting 10 days from the day following administration. Treatment with anti-asialo GM1 antibody never decreased the function of T lymphocytes measured by blastogenesis with phytohemagglutinin or T cell growth factor. The tumoricidal functions of activated macrophages but not of resident macrophages were decreased by in vivo treatment with anti-asialo GM1 antibody. The anti-asialo GM1 antibody was evaluated in terms of the enhancing effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1-2 weeks before the removal of primary tumor, when the tumor cells are thought to be released into blood circulation from the primary site. In addition, accelerated growth of transplanted tumors at the primary site was observed in mice treated with anti-asialo GM1 antibody. These results strongly suggest that anti-asialo GM1 antibody enhances the incidence of in vivo tumor metastases and the growth of transplanted tumor mainly by suppressing the function of NK cells. The maximum effective dose (MED) of mitomycin C or its derivative (M-83) suppressed NK activity significantly, and pretreatment with these anticancer agents enhanced the growth of the artificial pulmonary and liver metastases. In contrast, the MED of cDDP showed no effect on the NK activity or the numbers of pulmonary and liver metastases. These results indicate that the depression of NK activity induced by chemotherapy results in the promotion of metastatic disease. From these studies it can be concluded that NK cells have a key role in the control of metastases of malignant disease, and that support of NK activity is very important for the prevention of metastases.
通过使用抗去唾液酸GM1抗体和抗癌药物，在B16黑色素瘤细胞和C57BL/6小鼠中分析了肿瘤人工转移和自发转移的机制。单次给予500微克抗去唾液酸GM1抗体可导致C57BL/6小鼠脾细胞中NK活性显著降低，从给药后的第二天起持续10天。用抗去唾液酸GM1抗体处理从未降低通过植物血凝素或T细胞生长因子刺激增殖来测定的T淋巴细胞功能。体内用抗去唾液酸GM1抗体处理可降低活化巨噬细胞而非驻留巨噬细胞的杀肿瘤功能。就给药时间而言，评估了抗去唾液酸GM1抗体对肺转移的增强作用。在肿瘤接种前1天或接种当天用抗去唾液酸GM1抗体处理导致人工肺转移数量大幅增加。在自发转移的实验系统中，当在切除原发肿瘤前1 - 2周给予抗去唾液酸GM1抗体时，肺转移数量增加最为有效，此时肿瘤细胞被认为从原发部位释放到血液循环中。此外，在用抗去唾液酸GM1抗体处理的小鼠中观察到原发部位移植肿瘤生长加速。这些结果强烈表明，抗去唾液酸GM1抗体主要通过抑制NK细胞功能来提高体内肿瘤转移的发生率和移植肿瘤的生长。丝裂霉素C或其衍生物（M - 83）的最大有效剂量（MED）显著抑制NK活性，用这些抗癌药物预处理可增强人工肺转移和肝转移的生长。相比之下，顺铂的MED对NK活性或肺转移和肝转移数量没有影响。这些结果表明化疗诱导的NK活性降低导致转移性疾病的进展。从这些研究可以得出结论，NK细胞在控制恶性疾病转移中起关键作用，支持NK活性对预防转移非常重要。
