Autor(es):
Gregório, Ana C. ; Fonseca, Nuno A. ; Moura, Vera ; Lacerda, Manuela ; Figueiredo, Paulo ; Simões, Sérgio ; Dias, Sérgio ; Moreira, João Nuno
Data: 2016
Identificador Persistente: http://hdl.handle.net/10451/48721
Origem: Repositório da Universidade de Lisboa
Projeto/bolsa:
info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F51190%2F2010/PT;
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-BMA%2F121028%2F2010/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FNEU%2F04539%2F2013/PT;
Descrição
Copyright: © 2016 Gregório et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Ana Cristina Gregório is a student of the international PhD program in Experimental Biology and Biomedicine (PDBEB) from the Institute for Interdisciplinary Research, University of Coimbra and recipient of the fellowship SFRH/BD/51190/2010 from the Portuguese Foundation for Science and Technology (FCT). The work was supported by the grants PTDC/SAU-BMA/121028/2010 (FCT) and UID/NEU/04539/2013 (FEDER/COMPETE 2020/FCT).
