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

被引：94

作者：

Baklaushev, V. P. ^{[1
,2
]}

Kilpelainen, A. ^{[1
,3
]}

Petkov, S. ^{[3
]}

Abakumov, M. A. ^{[1
]}

Grinenko, N. F. ^{[1
]}

Yusubalieva, G. M. ^{[4
]}

Latanova, A. A. ^{[5
,6
]}

Gubskiy, I. L. ^{[1
]}

Zabozlaev, F. G. ^{[2
]}

Starodubova, E. S. ^{[5
,6
]}

Abakumova, T. O. ^{[4
]}

Isaguliants, M. G. ^{[3
,6
,7
,8
]}

Chekhonin, V. P. ^{[1
,4
]}

机构：

[1] Pirogov Russian Natl Res Med Univ, Minist Hlth Russian Federat, Res & Educ Ctr Med Nanobiotechnol, Moscow, Russia

[2] Fed Biomed Agcy Russian Federat, Fed Res & Clin Ctr Specialized Med Care & Med Tec, Moscow, Russia

[3] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden

[4] Minist Hlth Russian Federat, Dept Fundamental & Appl Neurobiol, Serbsky Natl Res Ctr Social & Forens Psychiat, Moscow, Russia

[5] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia

[6] Chumakov Fed Sci Ctr Res & Dev Immunobiol Prepara, Moscow, Russia

[7] NF Gamaleya Res Ctr Epidemiol & Microbiol, Moscow, Russia

[8] Riga Stradins Univ, Riga, Latvia

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

俄罗斯科学基金会;

关键词：

FIREFLY LUCIFERASE; IMMUNE-RESPONSE; TUMOR-GROWTH; METASTASIS; CELLS; MICROMETASTASIS; VISUALIZATION; CARCINOMA; MARKERS; MRI;

D O I：

10.1038/s41598-017-07851-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-mu m 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-gamma 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.

引用

页数：17

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