Caetano-Oliveira Rui, Gomes Marcos António, Abrantes Ana Margarida, Tavares-Silva Edgar, Oliveira Marco Carvalho, Laranjo Mafalda, Queirós Débora Basílio, Casalta-Lopes João, Pires Salomé, Carvalho Lina, Gouveia Rosa, Santos Paulo Rodrigues, Priolli Denise Gonçalves, Tralhão José Guilherme, Botelho Maria Filomena
Biophysics Unit, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Pathology Department, University Hospital (CHUC), Coimbra, Portugal.
Biophysics Unit, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Pathophysiology. 2018 Jun;25(2):89-99. doi: 10.1016/j.pathophys.2018.02.002. Epub 2018 Mar 13.
Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 10 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (Tc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.
结直肠癌（CRC）是西方国家第二常见且致命的癌症。由于缺乏合适的CRC模型，对其在结肠和直肠不同部位的发病率、基因特征以及这些因素如何导致局部/远处进展的生物学理解受到了阻碍。我们报告了一种可重复的模型，使用人类CRC细胞系（CL）（WiDr、LS1034、C2BBe1）（1×10个细胞/动物）注射到RNU大鼠（n = 55）体内，这些大鼠接受了盲肠造口术和降结肠造口术，并伴有乙状结肠黏膜皮肤瘘。通过免疫组织化学对CL进行特征分析：CK20、CDX2、P53、波形蛋白、Ki67、CD44、CD133、E-钙黏蛋白、β-连环蛋白和癌胚抗原（CEA）；研究了癌症干细胞与免疫系统的相互作用，并使用核医学成像（Tc-MIBI）评估肿瘤进展。动物发生了局部侵袭性肿瘤，并且记录到WiDr细胞系出现神经侵袭。在WiDr细胞系中检测到癌症干细胞（CD44阳性）。所有细胞系均刺激了免疫系统，其中WiDr细胞系最具侵袭性。成像研究显示肿瘤摄取。利用这个CRC模型，我们可以研究微环境的作用以及肿瘤与基质的相互作用。所有CL细胞系都引发了原发性疾病，但只有WiDR细胞系出现了神经侵袭，这可能代表一种转移途径。该模型有助于揭示潜在的转移机制，并最终测试针对CRC更好地治疗方法。
