Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) fin the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model

Several studies have indicated an interaction between tumor cells and infil trating 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 B AG human tumor xenograft, Subcutaneous tumor growth and lung metastasis wer e compared between wild-type immunodeficient mice and mice with the combine d deficiencies. Tumor growth was evaluated by volume measurements and plasm a P-galactosidase activity and metastasis was evaluated by counting lung su rface metastases, Although no differences appeared in primary tumor take be tween the two groups of mice, a significant difference was observed in prim ary tumor growth, with tumors in uPA(-/-) mice growing significantly more s lowly. In addition, a nonsignificant trend toward fewer lung metastases in uPA(-/-) mice was observed, The present data points to a critical role of s tromal-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 m ice was found.