Gewalt Tabea, Dmitrieva Anna M, Elsner Felix, Zhao Xinlei, Sieber Daniel Dimitri, Kocak Ilayda Gülsen, Yang Qian, Orschel Claudia Viktoria, Eckert Naja Maria, Goebel Bianca, Nill Marieke, Peter Franziska, Hartmann Arndt, Beleggia Filippo, Odenthal Margarete, Reinhardt Hans Christian, Ullrich Roland Tillmann, Graw Frederik, Meder Lydia
Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Chair of Experimental Medicine I, Medical Faculty, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Commun Biol. 2025 May 13;8(1):741. doi: 10.1038/s42003-025-08146-0.
Cre-recombinase inducible model systems are extensively used in cancer research to manipulate gene expression in specific tissues and induce autochthonous tumor growth. These systems often involve the cross-breeding of genetically engineered organisms containing loxP-flanked alleles with those expressing Cre-recombinase. This approach, while effective, has the challenge of requiring high numbers of animals due to breeding requirements. Other frequently used tumor induction methods in cancer research involve the direct application of viral Cre-recombinase vectors. This approach presents the challenge of the accessibility of facilities that meet the necessary safety level. In this context, we perform a comprehensive comparison between TAT-CRE (biosafety level S1) and adenoviral Cre-recombinase induced (biosafety level S2) lung adenocarcinomas driven by Kras expression and Trp53 depletion. We use in vivo lung tumor monitoring via computed tomography, single-cell RNA sequencing, immunohistochemistry and flow cytometry to elucidate similarities and differences between TAT-CRE and adenoviral Cre-recombinase induced lung adenocarcinomas. TAT-CRE induced lung tumors present differences in micro-vessels and macrophages but with corresponding tumor onset and growth characteristics compared to adenoviral-Cre recombinase induced lung tumors. Taken together, TAT-CRE is a valuable genetic engineering safety level S1 alternative for cancer induction and may be implemented in other cancer models than lung cancer.
Cre重组酶诱导模型系统在癌症研究中被广泛用于操纵特定组织中的基因表达并诱导原位肿瘤生长。这些系统通常涉及将含有loxP侧翼等位基因的基因工程生物与表达Cre重组酶的生物进行杂交。这种方法虽然有效，但由于繁殖要求，面临需要大量动物的挑战。癌症研究中其他常用的肿瘤诱导方法涉及直接应用病毒Cre重组酶载体。这种方法面临着需要具备必要安全水平设施的可及性挑战。在此背景下，我们对由Kras表达和Trp53缺失驱动的TAT-CRE（生物安全水平S1）诱导的肺腺癌和腺病毒Cre重组酶诱导的（生物安全水平S2）肺腺癌进行了全面比较。我们通过计算机断层扫描、单细胞RNA测序、免疫组织化学和流式细胞术对体内肺肿瘤进行监测，以阐明TAT-CRE诱导的肺腺癌和腺病毒Cre重组酶诱导的肺腺癌之间的异同。与腺病毒Cre重组酶诱导的肺肿瘤相比，TAT-CRE诱导的肺肿瘤在微血管和巨噬细胞方面存在差异，但具有相应的肿瘤发生和生长特征。综上所述，TAT-CRE是一种用于癌症诱导的有价值的生物安全水平S1基因工程替代方法，并且可能在肺癌以外的其他癌症模型中实施。
