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Title: Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model
Authors: Gregório, Ana C. 
Fonseca, Nuno A. 
Moura, Vera 
Lacerda, Manuela 
Figueiredo, Paulo
Simões, Sérgio 
Dias, Sérgio
Moreira, João Nuno 
Issue Date: 2016
Publisher: Public Library of Science
Project: SFRH/BD/51190/ 2010 
PTDC/SAU-BMA/121028/2010 (FCT) 
UID/NEU/04539/2013 (FEDER/COMPETE 2020/FCT) 
Serial title, monograph or event: PLoS ONE
Volume: 11
Issue: 11
Abstract: 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.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0165817
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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