Elliott B E, Ekblom P, Pross H, Niemann A, Rubin K
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
Cell Adhes Commun. 1994 Jan;1(4):319-32. doi: 10.3109/15419069409097263.
In the present report, we investigated the possible importance of beta 1 integrins in the growth and metastasis of a murine mammary carcinoma, SP1, and a metastatic variant, SP1-3M in vivo. CBA/J female mice bearing SP1 tumor transplants were injected with anti-beta 1 integrin IgG or control nonimmune IgG (200 micrograms per mouse; i.p.) every two days. Animals received anti-CD4 antibody (100 micrograms per mouse) at time zero to suppress immunity against rabbit IgG. Outgrowth of macroscopic metastases from SP1, but not from SP1-3M primary tumors, was markedly inhibited in animals receiving anti-beta 1 integrin IgG but not nonimmune IgG. To assess the stage(s) in the metastatic cascade affected, we examined the number and diameter of micrometastatic nodules in treated and untreated groups. The diameter of micrometastases was significantly reduced in SP1-tumor-bearing mice treated with anti-beta 1 integrin IgG compared to control IgG, although the number of nodules per cm2 of lung sections examined remained unchanged. No change in the number or size of micrometastases in SP1-3M tumor-bearing mice was observed. No difference in the binding, or complement-mediated and antibody-dependent cell-mediated cytotoxicity of anti-beta 1 integrin IgG with SP1 and SP1-3M cells was detected. The results suggest that under these conditions anti-beta 1 integrin inhibits metastatic tumor growth in lung tissue, but has minimal effect on intravasation, adhesion to target organs and extravasation.
在本报告中，我们研究了β1整合素在小鼠乳腺癌SP1及其转移变体SP1 - 3M体内生长和转移中的潜在重要性。每隔两天给携带SP1肿瘤移植的CBA/J雌性小鼠注射抗β1整合素IgG或对照非免疫IgG（每只小鼠200微克；腹腔注射）。动物在零时接受抗CD4抗体（每只小鼠100微克）以抑制对兔IgG的免疫反应。接受抗β1整合素IgG而非非免疫IgG的动物中，SP1原发性肿瘤的宏观转移灶生长明显受到抑制，但SP1 - 3M原发性肿瘤的转移灶未受抑制。为了评估转移级联反应中受影响的阶段，我们检查了治疗组和未治疗组微转移结节的数量和直径。与对照IgG相比，用抗β1整合素IgG治疗的携带SP1肿瘤的小鼠中微转移灶的直径显著减小，尽管每平方厘米肺切片检查的结节数量保持不变。在携带SP1 - 3M肿瘤的小鼠中未观察到微转移灶数量或大小的变化。未检测到抗β1整合素IgG与SP1和SP1 - 3M细胞的结合、补体介导的细胞毒性以及抗体依赖性细胞介导的细胞毒性存在差异。结果表明，在这些条件下，抗β1整合素抑制肺组织中转移性肿瘤的生长，但对肿瘤细胞进入血管、黏附到靶器官以及渗出的影响最小。
