Frandsen T L, Holst-Hansen C, Nielsen B S, Christensen I J, Nyengaard J R, Carmeliet P, Brünner N
The Fintsen Laboratory, Copenhagen University Hospital, Denmark.
Cancer Res. 2001 Jan 15;61(2):532-7.
Several studies have indicated an interaction between tumor cells and infiltrating stromal cells regarding the urokinase plasminogen activation (uPA) system. By developing combined uPA gene-disrupted and immunodeficient mice, we have studied the role of stromal uPA for the growth of the MDA-MB-435 BAG human tumor xenograft. Subcutaneous tumor growth and lung metastasis were compared between wild-type immunodeficient mice and mice with the combined deficiencies. Tumor growth was evaluated by volume measurements and plasma beta-galactosidase activity and metastasis was evaluated by counting lung surface metastases. Although no differences appeared in primary tumor take between the two groups of mice, a significant difference was observed in primary tumor growth, with tumors in uPA-/- mice growing significantly more slowly. In addition, a nonsignificant trend toward fewer lung metastases in uPA-/- mice was observed. The present data points to a critical role of stromal-derived uPA in the primary tumor growth of MDA-MB-435 BAG xenografts, whereas only a trend toward fewer lung metastases in uPA gene-disrupted mice was found.
多项研究表明，在尿激酶型纤溶酶原激活（uPA）系统方面，肿瘤细胞与浸润性基质细胞之间存在相互作用。通过培育uPA基因缺失与免疫缺陷相结合的小鼠，我们研究了基质uPA在MDA-MB-435 BAG人肿瘤异种移植瘤生长中的作用。比较了野生型免疫缺陷小鼠与联合缺陷小鼠的皮下肿瘤生长及肺转移情况。通过体积测量和血浆β-半乳糖苷酶活性评估肿瘤生长，通过计数肺表面转移灶评估转移情况。虽然两组小鼠在原发性肿瘤形成方面未出现差异，但在原发性肿瘤生长方面观察到显著差异，uPA基因敲除小鼠的肿瘤生长明显更缓慢。此外，观察到uPA基因敲除小鼠的肺转移有减少的趋势，但不显著。目前的数据表明，基质来源的uPA在MDA-MB-435 BAG异种移植瘤的原发性肿瘤生长中起关键作用，而在uPA基因敲除小鼠中仅发现肺转移有减少的趋势。
