Luo Yi, Chen Xiaohong, O'donnell Michael A
University of Iowa Department of Urology, Iowa City, Iowa 52242, USA.
J Urol. 2004 Dec;172(6 Pt 1):2414-20. doi: 10.1097/01.ju.0000143860.50878.b1.
Animal orthotopic tumor models are commonly used in bladder cancer studies. However, to our knowledge there is currently no accurate method to quantify tumor growth inside the bladder in living animals. We used prostate specific antigen (PSA) as a marker to cope with this limitation.
Infectious but replication incompetent retroviral particles carrying PSA coding sequence were constructed and infected into MB49 cells, a mouse bladder transitional cell carcinoma line of C57BL/6 origin. Syngeneic mice were intravesically implanted with the novel MB49-PSA transfectants. Tumor burden was evaluated by enzyme-linked immunosorbent assay measurement for PSA in urine and bladder tissues.
The MB49-PSA line actively secreted PSA in culture as well as in urine (18 to 2,062 pg/ml) depending on tumor mass. Immunofluorescence staining confirmed PSA expression in MB49-PSA derived orthotopic tumors. Urinary PSA production paralleled tumor growth and was detectable prior to the development of a palpable tumor. Although urinary PSA did not tightly correlate with tumor mass, all bladders (total of 16 tested) weighing 34 mg or greater (18 to 21 mg for age and sex matched normal bladders) showed 18 pg/ml or greater urinary PSA. In contrast, bladder tissue PSA correlated more with tumor mass in general and it was measurable even before the detection of urinary PSA. This MB49-PSA orthotopic tumor model also demonstrated its usefulness for evaluating the antibladder cancer agents gemcitabine and mitomycin.
This novel MB49-PSA line may serve as a useful tool for bladder cancer study because its growth inside the bladder can be noninvasively measured in living animals even during early stages of tumor growth.
动物原位肿瘤模型常用于膀胱癌研究。然而，据我们所知，目前尚无准确方法可量化活体动物膀胱内肿瘤的生长情况。我们使用前列腺特异性抗原（PSA）作为标志物来应对这一局限性。
构建携带PSA编码序列的感染性但无复制能力的逆转录病毒颗粒，并将其感染MB49细胞，MB49细胞是源自C57BL/6的小鼠膀胱移行细胞癌系。将同基因小鼠经膀胱内植入新型MB49-PSA转染细胞。通过酶联免疫吸附测定法检测尿液和膀胱组织中的PSA来评估肿瘤负荷。
MB49-PSA细胞系在培养物以及尿液中（18至2062 pg/ml）均能根据肿瘤大小主动分泌PSA。免疫荧光染色证实MB49-PSA衍生的原位肿瘤中存在PSA表达。尿PSA的产生与肿瘤生长平行，在可触及肿瘤形成之前即可检测到。尽管尿PSA与肿瘤大小并非紧密相关，但所有重量达34 mg或更大（年龄和性别匹配的正常膀胱为18至21 mg）的膀胱（共检测16个）尿PSA均显示为18 pg/ml或更高。相比之下，膀胱组织中的PSA总体上与肿瘤大小的相关性更强，甚至在检测到尿PSA之前即可测量。这种MB49-PSA原位肿瘤模型还证明了其在评估抗膀胱癌药物吉西他滨和丝裂霉素方面的实用性。
这种新型MB49-PSA细胞系可能是膀胱癌研究的有用工具，因为即使在肿瘤生长的早期阶段，也可在活体动物中无创测量其在膀胱内的生长情况。
