Ossowski L, Russo H, Gartner M, Wilson E L
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
J Cell Physiol. 1987 Nov;133(2):288-96. doi: 10.1002/jcp.1041330212.
Our aim was to identify conditions which would permit the development of spontaneous metastasis of a human tumor in nude mice in a rapid and predictable manner and to explore ways to quantitate metastasis. Using a human squamous carcinoma--HEp3--we determined that invasiveness and metastasis were influenced by the host. HEp3 cells grew very rapidly and without a significant lag period in Balb/c and NIH(S)-II nude mice kept in aseptic conditions; a much longer lag period was observed in NIH-Swiss mice kept in conventional conditions. The HEp3 tumor displayed a highly invasive behavior in N-NIH(S)-II mice, in which it invaded the body wall, gaining access to the peritoneal cavity. Microinvasion was noted in all strains of mice inoculated with HEp3 cells. To prolong survival of the mice until metastases became evident, primary tumors were excised when they weighed 1-2 gm. N-NIH(S)-II and Balb/c nude mice, maintained in germ-free conditions, were most receptive to the development of metastases-lung metastases developed in 80% of these mice. Over 60% of all metastases were present within 4 weeks following the removal of the primary. Only 26% of tumor bearing NIH-Swiss developed lung metastases. Lung metastases were observed in some mice in the absence of local microinvasion, local tumor recurrence, and regardless of the presence of lymph node involvement. They were also noted in mice from which primary tumors were not excised. We compared three methods of lung metastasis detection: histology, detection of tumor cells in the cultures of lung minces, and the measurement of the levels of human urokinase-type plasminogen activator directly in the lysates of lungs. The detection of tumor cells in cultures of lung minces appeared to be the most sensitive of these methods and the determination of enzyme in lung lysates seemed to hold most promise for a quantitative approach. These data indicate that, the type of tumor, as well as the genetic background and the maintenance conditions of the host, have to be carefully selected to ensure the successful outcome of the particular tumor-host interaction being studied. Adherence to these guidelines allowed us, in the case of the HEp3 tumor, to develop a rapid, predictable, and efficient model in which to study factors affecting metastasis of this human tumor.
我们的目标是确定能使人类肿瘤在裸鼠体内快速且可预测地发生自发性转移的条件，并探索定量转移的方法。使用人类鳞状细胞癌——HEp3——我们确定侵袭性和转移受宿主影响。在无菌条件下饲养的Balb/c和NIH(S)-II裸鼠中，HEp3细胞生长非常迅速且无明显滞后期；在常规条件下饲养的NIH-瑞士小鼠中观察到更长的滞后期。HEp3肿瘤在N-NIH(S)-II小鼠中表现出高度侵袭性行为，它侵入体壁，进入腹腔。在接种HEp3细胞的所有小鼠品系中均观察到微侵袭。为了延长小鼠存活时间直至转移明显，当原发性肿瘤重1 - 2克时将其切除。在无菌条件下饲养的N-NIH(S)-II和Balb/c裸鼠对转移的发生最敏感——这些小鼠中有80%发生了肺转移。超过60%的所有转移在原发性肿瘤切除后4周内出现。只有26%的荷瘤NIH-瑞士小鼠发生了肺转移。在一些小鼠中，即使没有局部微侵袭、局部肿瘤复发且无论有无淋巴结受累，也观察到了肺转移。在未切除原发性肿瘤的小鼠中也注意到了肺转移。我们比较了三种肺转移检测方法：组织学、肺碎块培养物中肿瘤细胞的检测以及直接在肺裂解物中测量人尿激酶型纤溶酶原激活剂的水平。肺碎块培养物中肿瘤细胞的检测似乎是这些方法中最敏感的，而肺裂解物中酶的测定似乎对定量方法最有前景。这些数据表明，必须仔细选择肿瘤类型以及宿主的遗传背景和饲养条件，以确保所研究的特定肿瘤 - 宿主相互作用取得成功结果。遵循这些指导原则使我们在HEp3肿瘤的情况下，能够建立一个快速、可预测且有效的模型来研究影响这种人类肿瘤转移的因素。
