Sakakibara T, Xu Y, Bumpers H L, Chen F A, Bankert R B, Arredondo M A, Edge S B, Repasky E A
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA.
Cancer J Sci Am. 1996 Sep-Oct;2(5):291-300.
We have studied the growth and metastatic potential of surgical specimens of breast carcinomas engrafted into the large abdominal (gonadal) fat pad of severe combined immunodeficient (SCID) mice. We present results of this study, details of the implantation protocol and histologic characterization of several of the tumor xenografts.
We evaluated the growth within SCID mice of 48 breast carcinoma specimens derived from 46 patients (45 primary breast cancers or local recurrences and 3 regional metastatic lymph nodes) obtained from resected tissues at this Institute over a 3-year period. The growth of each transplant was assessed by histologic examination of the xenografts at various times after implantation or upon passage into additional mice.
We observed that placement of human breast tumors within the gonadal fat pad could result in tumors that grew either rapidly, slowly, or not at all. Of 48 tumors studied, 12 (25%), including one of the three lymph node-derived tumors, grew rapidly enough within some or all of the implanted mice (i.e., the tumors reached a diameter of 2-3 cm within 2-6 months) to allow repeated passage. Metastatic spread to the SCID mouse lung, liver, and/or diaphragm and other sites was observed with the xenografts derived from 8 of these 12 rapidly growing tumors. Tumors in a second category often took from 6 months to over 1 year to only double or triple in size. This slow-growth group consisted of 25 patients' tumors (53%), including the remaining two metastatic lymph node-derived tumors. These xenografts would usually maintain a slow growth rate even upon later passage into new animals. A third category consisted ofpatients' tumors (23%) that failed to grow at all (i.e., no evidence of tumor growth in any of the mice implanted), as discerned by histologic evaluation at various times after implantation. Histologic examination of tumor xenografts and metastatic tumors revealed considerable variation in histopathology among the different patients' tumors.
Further examination of the heterogeneous properties of primary human breast carcinomas within SCID mice may provide a simple yet valuable new approach for the long-term study of human breast cancer biology. Importantly, use of the protocol described here can often permit the isolation of substantial quantities of human breast cancer cells for biochemical and molecular analyses. The ability to passage patients' breast tumors into large numbers of mice will permit the preclinical testing of new therapies for the treatment and prevention of this disease.
我们研究了移植到严重联合免疫缺陷（SCID）小鼠大腹部（性腺）脂肪垫中的乳腺癌手术标本的生长和转移潜能。我们展示了这项研究的结果、植入方案的细节以及几种肿瘤异种移植的组织学特征。
我们评估了48个乳腺癌标本在SCID小鼠体内的生长情况，这些标本取自本研究所3年期间切除的组织，来自46例患者（45例原发性乳腺癌或局部复发癌以及3例区域转移性淋巴结）。通过在植入后不同时间或传代至其他小鼠后对异种移植瘤进行组织学检查，评估每个移植瘤的生长情况。
我们观察到将人乳腺肿瘤置于性腺脂肪垫内可导致肿瘤生长迅速、缓慢或根本不生长。在研究的48个肿瘤中，12个（25%），包括3个淋巴结来源的肿瘤中的1个，在部分或全部植入小鼠体内生长迅速（即肿瘤在2 - 6个月内直径达到2 - 3厘米），从而允许重复传代。在这12个快速生长的肿瘤中，有8个的异种移植瘤出现了向SCID小鼠肺、肝和/或膈肌及其他部位的转移扩散。第二类肿瘤通常需要6个月至1年以上时间，大小仅增长一倍或两倍。这个生长缓慢的组包括25例患者的肿瘤（53%），包括其余两个淋巴结来源的转移性肿瘤。这些异种移植瘤即使后来传代至新动物，通常也会保持缓慢的生长速度。第三类包括患者的肿瘤（23%），在植入后不同时间通过组织学评估发现根本不生长（即在任何植入的小鼠中均无肿瘤生长迹象）。对肿瘤异种移植瘤和转移性肿瘤的组织学检查显示，不同患者的肿瘤在组织病理学上存在相当大的差异。
进一步研究原发性人乳腺癌在SCID小鼠体内的异质性特性，可能为长期研究人乳腺癌生物学提供一种简单而有价值的新方法。重要的是，使用这里描述 的方案通常可以分离出大量人乳腺癌细胞用于生化和分子分析。将患者的乳腺肿瘤传代至大量小鼠的能力将允许对治疗和预防这种疾病的新疗法进行临床前测试。
