Karr J F, Kantor J A, Hand P H, Eggensperger D L, Schlom J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 1995 Jun 1;55(11):2455-62.
Human prostate-specific antigen (PSA) has been shown as an aid in the early detection of prostate cancer (W. J. Catalona et al., J. Am. Med. Assoc., 270: 948-954, 1993) and was approved in 1994 by the Food and Drug Administration for early detection of prostate cancer. Immunotherapies directed against PSA have been suggested in patients with metastatic prostate cancer. One of the essential questions is to define which nonhuman species express PSA for experimental studies. Using Southern blot analyses, genes related to human PSA have been detected in several nonhuman primate species, including chimpanzee, orangutan, gorilla, macaque, and rhesus monkey, but not in other mammalian species, including rabbit, cow, pig, dog, rat, or mouse. Immunohistochemical staining with anti-human PSA antisera detected strong staining in both human and monkey prostatic epithelial cells with no reactivity to rat prostate cells. Because the PSA gene is not present in the murine genome, a matched set of murine cell lines has been developed that may be useful to study the biochemical functions of PSA and as an experimental target for PSA-directed immunotherapy. To establish such cell lines, a C57BL/6 murine colon adenocarcinoma cell line, MC-38, was transfected with a retroviral vector containing cDNA encoding the human PSA gene. Genetic analysis of a PSA-secreting clone, PSA/MC-38, demonstrated that the PSA gene had been stably integrated into the MC-38 genome. The PSA/MC-38 cell line was found to secrete PSA into tissue culture medium, producing a protein of approximately M(r) 30,000. In vivo, PSA/MC-38 grew as a s.c. tumor in male and female mice. PSA/MC-38 tumors grew more rapidly in athymic mice than in syngeneic C57BL/6 mice, and in both mouse strains, the PSA/MC-38 tumors grew more slowly than control vector-transduced tumors. PSA was detected in the serum and tumors of PSA/MC-38 tumor-bearing mice. It is proposed that PSA/MC-38 cells may be used as a murine tumor model to test potential therapeutic vaccines and other experimental therapies directed against PSA.
人类前列腺特异性抗原（PSA）已被证明有助于前列腺癌的早期检测（W. J. 卡塔洛纳等人，《美国医学会杂志》，270: 948 - 954, 1993），并于1994年被美国食品药品监督管理局批准用于前列腺癌的早期检测。对于转移性前列腺癌患者，已有人提出针对PSA的免疫疗法。一个关键问题是确定哪些非人类物种表达PSA以用于实验研究。通过Southern印迹分析，在包括黑猩猩、猩猩、大猩猩、猕猴和恒河猴在内的几种非人类灵长类物种中检测到了与人类PSA相关的基因，但在包括兔子、牛、猪、狗、大鼠或小鼠在内的其他哺乳动物物种中未检测到。用抗人PSA抗血清进行免疫组织化学染色显示，在人和猴的前列腺上皮细胞中均有强染色，而对大鼠前列腺细胞无反应。由于PSA基因不存在于小鼠基因组中，因此已构建了一组匹配的小鼠细胞系，这可能有助于研究PSA的生化功能，并作为PSA导向免疫疗法的实验靶点。为了建立这样的细胞系，用含有编码人PSA基因的cDNA的逆转录病毒载体转染C57BL/6小鼠结肠腺癌细胞系MC - 38。对一个分泌PSA的克隆PSA/MC - 38进行基因分析表明，PSA基因已稳定整合到MC - 38基因组中。发现PSA/MC - 38细胞系可将PSA分泌到组织培养基中，产生一种分子量约为30,000的蛋白质。在体内，PSA/MC - 38在雄性和雌性小鼠中均以皮下肿瘤的形式生长。PSA/MC - 38肿瘤在无胸腺小鼠中比在同基因C57BL/6小鼠中生长得更快，并且在这两种小鼠品系中，PSA/MC - 38肿瘤比对照载体转导的肿瘤生长得更慢。在携带PSA/MC - 38肿瘤的小鼠的血清和肿瘤中检测到了PSA。有人提出，PSA/MC - 38细胞可作为一种小鼠肿瘤模型，用于测试针对PSA的潜在治疗性疫苗和其他实验性疗法。
