Segatto Natália V, Simões Lucas D, Bender Camila B, Sousa Fernanda S, Oliveira Thais L, Paschoal Júlia D F, Pacheco Bruna S, Lopes Isadora, Seixas Fabiana K, Qazi Aisha, Thomas Faith M, Chaki Sulalita, Robertson Noah, Newsom Jordan, Patel Shovik, Rund Laurie A, Jordan Luke R, Bolt Courtni, Schachtschneider Kyle M, Schook Lawrence B, Collares Tiago V
Technology Development Center, Laboratory of Cancer Biotechnology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
Department of Animal Sciences, University of Illinois, Urbana, IL, United States.
Front Oncol. 2024 Feb 26;14:1323422. doi: 10.3389/fonc.2024.1323422. eCollection 2024.
Bladder cancer is a common neoplasia of the urinary tract that holds the highest cost of lifelong treatment per patient, highlighting the need for a continuous search for new therapies for the disease. Current bladder cancer models are either imperfect in their ability to translate results to clinical practice (mouse models), or rare and not inducible (canine models). Swine models are an attractive alternative to model the disease due to their similarities with humans on several levels. The Oncopig Cancer Model has been shown to develop tumors that closely resemble human tumors. However, urothelial carcinoma has not yet been studied in this platform.
We aimed to develop novel Oncopig bladder cancer cell line (BCCL) and investigate whether these urothelial swine cells mimic human bladder cancer cell line (5637 and T24) treatment-responses to cisplatin, doxorubicin, and gemcitabine in vitro.
Results demonstrated consistent treatment responses between Oncopig and human cells in most concentrations tested (p>0.05). Overall, Oncopig cells were more predictive of T24 than 5637 cell therapeutic responses. Microarray analysis also demonstrated similar alterations in expression of apoptotic (GADD45B and TP53INP1) and cytoskeleton-related genes (ZMYM6 and RND1) following gemcitabine exposure between 5637 (human) and Oncopig BCCL cells, indicating apoptosis may be triggered through similar signaling pathways. Molecular docking results indicated that swine and humans had similar Dg values between the chemotherapeutics and their target proteins.
Taken together, these results suggest the Oncopig could be an attractive animal to model urothelial carcinoma due to similarities in in vitro therapeutic responses compared to human cells.
膀胱癌是泌尿系统常见的肿瘤，每位患者的终身治疗成本最高，这凸显了持续寻找该疾病新疗法的必要性。目前的膀胱癌模型要么在将结果转化为临床实践方面存在缺陷（小鼠模型），要么罕见且不可诱导（犬类模型）。猪模型因其在多个层面与人类相似，是模拟该疾病的有吸引力的替代方案。已证明Oncopig癌症模型会发展出与人类肿瘤极为相似的肿瘤。然而，该平台尚未对尿路上皮癌进行研究。
我们旨在开发新型Oncopig膀胱癌细胞系（BCCL），并研究这些尿路上皮猪细胞在体外对顺铂、阿霉素和吉西他滨的治疗反应是否与人类膀胱癌细胞系（5637和T24）相似。
结果表明，在大多数测试浓度下，Oncopig细胞和人类细胞的治疗反应一致（p>0.05）。总体而言，Oncopig细胞比5637细胞对T24细胞治疗反应的预测性更强。微阵列分析还表明，5637（人类）和Oncopig BCCL细胞在吉西他滨暴露后，凋亡相关基因（GADD45B和TP53INP1）和细胞骨架相关基因（ZMYM6和RND1）的表达变化相似，表明可能通过相似的信号通路触发凋亡。分子对接结果表明，猪和人类的化疗药物与其靶蛋白之间的Dg值相似。
综上所述，这些结果表明，由于与人类细胞在体外治疗反应方面存在相似性，Oncopig可能是模拟尿路上皮癌的有吸引力的动物模型。
