Katz Matthew H, Takimoto Shinako, Spivack Daniel, Moossa A R, Hoffman Robert M, Bouvet Michael
Department of Surgery, University of California at San Diego, San Diego, California 92161, USA.
Clin Exp Metastasis. 2004;21(1):7-12. doi: 10.1023/b:clin.0000017160.93812.3b.
In order to investigate the antitumor and antimetastatic efficacy of new chemotherapeutic agents, a novel, red-fluorescent, orthotopic model of pancreatic cancer was constructed in nude mice. MIA-PaCa-2 human pancreatic cancer cells were transduced with red fluorescent protein (RFP) and initially grown subcutaneously. Fluorescent tumor fragments were then transplanted onto the pancreas by surgical orthotopic implantation (SOI), facilitating high-resolution, real-time visualization of tumor and metastatic growth and dissemination in vivo. Tumor growth at the primary site was visible within the first postoperative week, while distant metastasis and the development of ascites became visible over the following week. This MIA-PaCa-2-RFP model produced extensive local disease and metastases to the retroperitoneum (100%), spleen (100%), intestinal and periportal lymph nodes (100%), liver (40%) and diaphragm (80%), and gave rise to malignant ascites and peritoneal carcinomatosis in 80% of cases. Growth and metastasis of tumor was more rapid and frequent than in previously described orthotopic pancreatic cancer models, leading to a median survival of only 21 days after tumor implantation. This unique, red fluorescent model rapidly and reliably simulates the highly aggressive course of human pancreatic cancer and can be easily non-invasively visualized in the live animal. The model can therefore be used for the discovery and evaluation of novel therapeutics for the treatment of this devastating disease.
为了研究新型化疗药物的抗肿瘤和抗转移疗效，在裸鼠中构建了一种新型的、红色荧光原位胰腺癌模型。将红色荧光蛋白（RFP）转导至MIA-PaCa-2人胰腺癌细胞中，并首先在皮下培养。然后通过手术原位植入（SOI）将荧光肿瘤片段移植到胰腺上，便于在体内对肿瘤及转移生长和播散进行高分辨率实时可视化观察。术后第一周即可观察到原发部位的肿瘤生长，而在接下来的一周内可观察到远处转移和腹水形成。该MIA-PaCa-2-RFP模型产生广泛的局部病变，并转移至腹膜后（100%）、脾脏（100%）、肠及门静脉周围淋巴结（100%）、肝脏（40%）和膈肌（80%），80%的病例出现恶性腹水和腹膜癌。与先前描述的原位胰腺癌模型相比，该模型肿瘤的生长和转移更快且更频繁，肿瘤植入后中位生存期仅为21天。这种独特的红色荧光模型能快速、可靠地模拟人类胰腺癌的高度侵袭性病程，并且可以在活体动物中轻松地进行非侵入性可视化观察。因此，该模型可用于发现和评估治疗这种毁灭性疾病的新型疗法。
