Pretlow T G, Wolman S R, Micale M A, Pelley R J, Kursh E D, Resnick M I, Bodner D R, Jacobberger J W, Delmoro C M, Giaconia J M
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
J Natl Cancer Inst. 1993 Mar 3;85(5):394-8. doi: 10.1093/jnci/85.5.394.
Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable.
Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts.
Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors.
Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts.
A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available.
Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation.
前列腺癌是美国男性中最常见的浸润性癌症，也是癌症死亡的第二大常见原因。1991年以前，将原发性前列腺癌从原发肿瘤传代培养超过3个月的尝试，在体内和体外均未成功，仅有极少数例外情况。1991年，我们报告了10例人类原发性前列腺癌中有6例在移植后约2 - 6个月建立了生长缓慢的肿瘤。然而，这些肿瘤均未超过5毫米，也无法连续传代移植。
本研究的目的是确定人类原发性前列腺癌是否能够生长为可连续传代移植的异种移植物。
从20例患者经尿道前列腺切除术或全前列腺切除术中获取的原发性前列腺癌细胞，在手术当天皮下注射到雄性裸鼠体内。在肿瘤移植前2 - 24天以及每隔10 - 12周，将缓释睾酮丸剂皮下植入小鼠体内。后续各代小鼠的连续移植采用类似方法进行。对6个肿瘤进行了染色体分析。
20例原发性前列腺癌中有6例生长到足以允许连续移植到第二代小鼠体内；其中4例在第二代小鼠中经组织病理学证实，并连续移植到三只或更多只连续的小鼠体内。当通过相同程序将单个原发性肿瘤注射到几只小鼠体内时，一些受体中的肿瘤未能生长，但在其他受体中可连续移植。这些肿瘤生长缓慢且不规则，经常出现消退。在手术当天开始对10个肿瘤进行短期培养，其中8个肿瘤同时注射到小鼠体内；成功连续移植的CWR31在培养中仅表现出异常中期，并显示出克隆性染色体变化。包括CWR31在内，成功进行染色体分析的6个肿瘤中有3个包含克隆性畸变。对严重联合免疫缺陷（SCID）小鼠进行的初步研究表明，在建立可连续传代移植的前列腺癌异种移植物方面，它们并不优于裸鼠。
一部分人类原发性前列腺癌可以生长为异种移植物。目前我们实验室正在传代培养4种新的可连续传代移植的异种移植物（CWR21、CWR31、CWR91和CWR22），这是以前所没有的资源。
我们的经验表明，连续移植中最重要的因素是泌尿外科医生和病理科医生在加快将肿瘤置于冷盐水中、检查冰冻切片以及移植方面的协作。
