Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model.
4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas. The drastic reduction of the number of inoculated cells resulted in increased tumor doubling times and decreased specific growth rates, following a Gompertzian tumor expansion. The established conditions for the 4T1 mouse model were further validated in a therapeutic study with peguilated liposomal doxorubicin, in clinical used in the setting of metastatic breast cancer. Inoculated cell density was proven to be a key methodological aspect towards the reproducible development of macrometastases in the 4T1 mouse model and a more reliable pre-clinical assessment of antimetastatic therapies.
CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.|IIIUC-Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Ana C
AC
Gregório
CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.|FFUC-Faculty of Pharmacy, Pólo das Ciências da Saúde, University of Coimbra, Coimbra, Portugal.
Nuno A
NA
Fonseca
CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.|TREAT U, SA, Coimbra, Portugal.
Vera
V
Moura
IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Manuela
M
Lacerda
IPOFG-EPE-Portuguese Institute of Oncology Francisco Gentil, Coimbra, Portugal.
Paulo
P
Figueiredo
CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.|FFUC-Faculty of Pharmacy, Pólo das Ciências da Saúde, University of Coimbra, Coimbra, Portugal.
Sérgio
S
Simões
IMM-Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Sérgio
S
Dias
CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.|FFUC-Faculty of Pharmacy, Pólo das Ciências da Saúde, University of Coimbra, Coimbra, Portugal.
João Nuno
JN
Moreira
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D011092:Polyethylene Glycols / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin