Ossowski L, Russo-Payne H, Wilson E L
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
Cancer Res. 1991 Jan 1;51(1):274-81.
Nude mice given inoculations s.c. of a human squamous carcinoma--HEp3 (1.5 x 10(6) cells/mouse)--developed invasive tumors that produced high levels of urokinase-type plasminogen activator (uPA) and metastasized predictably to the lungs and lymph nodes of the host. To investigate the role of uPA in invasion and metastasis, mice given inoculations of tumor cells were treated daily with s.c. injections of specific, anti-human uPA antibodies (rabbit polyclonal, 150 inhibitory units; mouse monoclonal, 3000 inhibitory units/mouse/day). Control mice received either saline or preimmune rabbit immunoglobulins. A total of approximately 50 mice was studied. The tumors were surgically excised 10 to 17 days postinoculation when weighing 1 to 2 g. Antibody administration was discontinued after tumor excision. Two strategies were used: (a) following the removal of tumors the mice were maintained and observed until respiratory distress, indicative of lung metastasis, was evident; or (b) their lungs were examined for evidence of metastasis on the day of tumor removal. While histological sections of s.c. tumors excised from control mice indicated extensive local invasion, evidence of invasion was absent in most tumors excised from mice in which tumor uPA was inhibited by the antibody (P less than 0.025). The inhibition of local invasion did not, however, lead to a reduced incidence of distant metastasis. Since we found that the presence of HEp3 tumors in mice elicits a pronounced granulocytosis, we propose that this response may facilitate the spread of tumor cells by a mechanism independent of endogenous tumor proteases.
给裸鼠皮下接种人鳞状细胞癌HEp3（1.5×10⁶个细胞/只小鼠）后，它们长出了侵袭性肿瘤，这些肿瘤产生高水平的尿激酶型纤溶酶原激活剂（uPA），并可预测地转移至宿主的肺和淋巴结。为了研究uPA在侵袭和转移中的作用，给接种肿瘤细胞的小鼠每天皮下注射特异性抗人uPA抗体（兔多克隆抗体，150个抑制单位；鼠单克隆抗体，3000个抑制单位/只小鼠/天）进行治疗。对照小鼠接受生理盐水或免疫前兔免疫球蛋白。共研究了约50只小鼠。接种后10至17天，当肿瘤重量达到1至2克时，将肿瘤手术切除。肿瘤切除后停止抗体给药。采用了两种策略：(a) 切除肿瘤后，维持并观察小鼠，直到出现呼吸窘迫（表明发生肺转移）；或(b) 在切除肿瘤当天检查其肺部有无转移迹象。虽然从对照小鼠切除的皮下肿瘤组织切片显示有广泛的局部侵袭，但在从抗体抑制肿瘤uPA的小鼠切除的大多数肿瘤中，没有侵袭迹象（P<0.025）。然而，局部侵袭的抑制并未导致远处转移发生率降低。由于我们发现小鼠体内HEp3肿瘤的存在会引发明显的粒细胞增多，我们提出这种反应可能通过一种独立于内源性肿瘤蛋白酶的机制促进肿瘤细胞的扩散。
