免疫缺陷动物在肿瘤细胞侵袭研究中的应用

近10余年来利用免疫缺陷动物从不同角度进行了人类瘤细胞侵袭性的观察。共进行了以下几个方面的工作:(1)侵袭模型的建立:共建立了6个体内侵袭模型(包括背侧皮下,肌肉内,腹腔内,肾包膜下,睾丸包膜下和爪垫皮下等移植侵袭模型),不同模型具有不同用途。这6种侵袭模型均可作侵袭力的比较研究。(2)侵袭和转移之间关系的观察;利用爪垫皮下和睾丸包膜下移植侵袭模型,以不同时间截肢(切除局部肿瘤),待动物存活到最终时间和不同时间处死动物,观察局部肿瘤侵袭程度和转移出现时间的关系。初步证明局部肿瘤侵袭发展到Ⅲ级侵袭以上时方出现转移,侵袭Ⅲ级是危险期,这个结果对临床肿瘤病人手术时机的选择有重要参考价值。(3)对瘤细胞侵袭程度的定量分析做了初步观察,为今后深入研究侵袭定量打下了基础。(4)瘤细胞侵袭性和器官微环境关系的观察,初步证明了肿瘤细胞侵袭性和转移一样,也具有器官特异性。(5)同时也证明了瘤细胞侵袭的表达与移植方式的关系,找出了对瘤细胞侵袭最敏感的部位和器官,如肾包膜下和腹腔内为敏感的部位;背侧部皮下为不敏感的部位。因此鉴定一个肿瘤是否具有侵袭性,其侵袭程度如何,就不能仅用一个部位和器官。本文总结了近10余年的初步结果,提出了一些待深入研究的问题,这为今后深入研究人类肿瘤细胞侵袭机制和实验治疗,建立了良好的基础和条件。

APPLICATION OF IMMUNODEFICIENCY ANIMAL IN THE STUDY OF TUMOR INVASION

In recent 10 years, we have employed immuno-deficiency animal to observe the invasiveness of human tumors from different point of view. In summary, the following works were undertaken. (1) Establishment of animal models of invasion, six in vivo iuvasion models were set up,including dorsal-lateral subcutaneous, intramuscular, intra-peritoneal, subrenal capsule, subtesticular capsule and footpadal subcutaneous imptantation. These models could be used for different purpose. All the six models could be employed for comparative study of tumor invasiveness. (2) Observation on the relationship between invasion and metastasis. The footpadal subcutaneous implantation model was used in the study. Local tumor was eradicated at different time interval. The relationship between local invasion and metastasis of tumor were inve-stigatedeither by sacrifying the animal at different time or after keeping the animal as long as they could survive. Our results indicate that metastasis can form only after local invasion reached Ⅲ-degree. So Ⅲ-degree local invasion is the critical stage. (3) Primary evaluation of quantitation of tumor invasion. (4) Observation on the relationship between the invasiveness of tumor cells and organ microenviroment. The results suggested the invasiveness of tumor cells, like metastasis of them, is also organspecific. (5) Our investigation also proved that the expression of tumor cell invasion is closely related with the ways they were implanted. In a word, our experimental results in 10 years were summed up and analysed. Problems worth further investigation was raised. These observations lay good foundation for further study of the mechanism and experimental treatment of tumor cell invasion.