AntiCancer, Inc., San Diego, CA, U.S.A.
Department of Surgery, University of California, San Diego, CA, U.S.A.
Anticancer Res. 2022 Feb;42(2):739-743. doi: 10.21873/anticanres.15532.
BACKGROUND/AIM: Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) model. An important goal of PDOX-model development is facile visualization of metastasis in live mice. In the present report we evaluated tumor growth and metastasis in pancreatic cancer PDOX NOG [Non-obese diabetes (NOD)/Scid/IL2Rγ]-and nude-mouse models using red fluorescent protein (RFP)-expressing tumor stroma to visualize the primary tumor and metastasis.
A patient-derived pancreatic cancer was initially implanted in transgenic RFP-expressing nude mice. Then, tumor fragments, which acquired RFP expressing stroma while growing in RFP-expressing nude mice were orthotopically implanted in nude and NOG mice. The primary pancreatic tumor and metastasis were observed 8 weeks after implantation.
Lymph-node metastases expressing red fluorescence were detected only in NOG mice. Significantly faster growth of primary pancreatic tumors and a higher incidence of lymph-node metastasis occurred in NOG mice compared to nude mice.
RFP-expressing tumor stroma, which traffics together with cancer cells to lymph nodes, is useful to observe tumor behavior, such as lymph-node metastasis in a PDOX NOG-mouse model which can be used for evaluation of novel anti-metastatic agents, as well as personalized therapy to identify effective drugs.
背景/目的:我们的实验室率先开发了患者来源的原位异种移植(PDOX)模型。PDOX 模型开发的一个重要目标是便于在活鼠体内可视化转移。在本报告中,我们使用表达红色荧光蛋白(RFP)的肿瘤基质来可视化原发性肿瘤和转移,评估了胰腺癌细胞 PDOXNOG [非肥胖型糖尿病(NOD)/ Scid/IL2Rγ]-和裸鼠模型中的肿瘤生长和转移。
最初将患者来源的胰腺癌植入转基因 RFP 表达裸鼠中。然后,在表达 RFP 的裸鼠中生长时获得表达 RFP 基质的肿瘤碎片被原位植入裸鼠和 NOG 小鼠中。植入 8 周后观察原发性胰腺肿瘤和转移。
仅在 NOG 小鼠中检测到表达红色荧光的淋巴结转移。与裸鼠相比,NOG 小鼠中原发性胰腺肿瘤的生长速度明显更快,淋巴结转移的发生率更高。
与癌细胞一起转移到淋巴结的表达 RFP 的肿瘤基质,可用于观察肿瘤行为,如 PDOXNOG 小鼠模型中的淋巴结转移,可用于评估新型抗转移药物以及用于识别有效药物的个性化治疗。