Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer

作者：Владимир П. Баклаушев, Athina Kilpeläinen, Stefan Petkov, Maxim A. Abakumov, N. F. Grinenko, Gaukhar M. Yusubalieva, Anastasia A. Latanova, Ilya L Gubskiy, Fedor Zabozlaev, Elizaveta S. Starodubova, Tatiana O. Abakumova, Maria G. Isaguliants, Vladimir Pavlovich Chekhonin · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/s41598-017-07851-z · 被引用次数：132 · 研究领域：bioluminescence and chemiluminescence research、Cancer Research and Treatments、Immunotherapy and Immune Responses

Implantation of reporter-labeled tumor cells in an immunocompetent host involves a risk of their immune elimination. We have studied this effect in a mouse model of breast cancer after the orthotopic implantation of mammary gland adenocarcinoma 4T1 cells genetically labelled with luciferase (Luc). Mice were implanted with 4T1 cells and two derivative Luc-expressing clones 4T1luc2 and 4T1luc2D6 exhibiting equal in vitro growth rates. In vivo, the daughter 4T1luc2 clone exhibited nearly the same, and 4T1luc2D6, a lower growth rate than the parental cells. The metastatic potential of 4T1 variants was assessed by magnetic resonance, bioluminescent imaging, micro-computed tomography, and densitometry which detected 100-μm metastases in multiple organs and bones at the early stage of their development. After 3-4 weeks, 4T1 generated 11.4 ± 2.1, 4T1luc2D6, 4.5 ± 0.6; and 4T1luc2, <1 metastases per mouse, locations restricted to lungs and regional lymph nodes. Mice bearing Luc-expressing tumors developed IFN-γ response to the dominant CTL epitope of Luc. Induced by intradermal DNA-immunization, such response protected mice from the establishment of 4T1luc2-tumors. Our data show that natural or induced cellular response against the reporter restricts growth and metastatic activity of the reporter-labelled tumor cells. Such cells represent a powerful instrument for improving immunization technique for cancer vaccine applications.