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

Abstract 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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: V. P. Baklaushev, A. Kilpeläinen, S. Petkov, M. A. Abakumov, N. F. Grinenko, G. M. Yusubalieva, A. A. Latanova, I. L. Gubskiy, F. G. Zabozlaev, E. S. Starodubova, T. O. Abakumova, M. G. Isaguliants, V. P. Chekhonin
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/1e8e0eebf76b4e3cbb74e7a11e8b17f1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:1e8e0eebf76b4e3cbb74e7a11e8b17f1
record_format dspace
spelling oai:doaj.org-article:1e8e0eebf76b4e3cbb74e7a11e8b17f12021-12-02T15:06:08ZLuciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer10.1038/s41598-017-07851-z2045-2322https://doaj.org/article/1e8e0eebf76b4e3cbb74e7a11e8b17f12017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07851-zhttps://doaj.org/toc/2045-2322Abstract 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.V. P. BaklaushevA. KilpeläinenS. PetkovM. A. AbakumovN. F. GrinenkoG. M. YusubalievaA. A. LatanovaI. L. GubskiyF. G. ZabozlaevE. S. StarodubovaT. O. AbakumovaM. G. IsaguliantsV. P. ChekhoninNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
V. P. Baklaushev
A. Kilpeläinen
S. Petkov
M. A. Abakumov
N. F. Grinenko
G. M. Yusubalieva
A. A. Latanova
I. L. Gubskiy
F. G. Zabozlaev
E. S. Starodubova
T. O. Abakumova
M. G. Isaguliants
V. P. Chekhonin
Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
description Abstract 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.
format article
author V. P. Baklaushev
A. Kilpeläinen
S. Petkov
M. A. Abakumov
N. F. Grinenko
G. M. Yusubalieva
A. A. Latanova
I. L. Gubskiy
F. G. Zabozlaev
E. S. Starodubova
T. O. Abakumova
M. G. Isaguliants
V. P. Chekhonin
author_facet V. P. Baklaushev
A. Kilpeläinen
S. Petkov
M. A. Abakumov
N. F. Grinenko
G. M. Yusubalieva
A. A. Latanova
I. L. Gubskiy
F. G. Zabozlaev
E. S. Starodubova
T. O. Abakumova
M. G. Isaguliants
V. P. Chekhonin
author_sort V. P. Baklaushev
title Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
title_short Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
title_full Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
title_fullStr Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
title_full_unstemmed Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
title_sort luciferase expression allows bioluminescence imaging but imposes limitations on the orthotopic mouse (4t1) model of breast cancer
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/1e8e0eebf76b4e3cbb74e7a11e8b17f1
work_keys_str_mv AT vpbaklaushev luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT akilpelainen luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT spetkov luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT maabakumov luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT nfgrinenko luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT gmyusubalieva luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT aalatanova luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT ilgubskiy luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT fgzabozlaev luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT esstarodubova luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT toabakumova luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT mgisaguliants luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
AT vpchekhonin luciferaseexpressionallowsbioluminescenceimagingbutimposeslimitationsontheorthotopicmouse4t1modelofbreastcancer
_version_ 1718388564603961344