Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model

• Autor: Gregório, Ana C ; Fonseca, Nuno A ; Moura, Vera ; Lacerda, Manuela ; Figueiredo, Paulo ; Simões, Sérgio ; Dias, Sérgio ; Moreira, João Nuno
• Sun, Lu-Zhe
• Assuntos: Analysis ; Animal models ; Animals ; Antibiotics, Antineoplastic - pharmacology ; Biology ; Biology and Life Sciences ; Brain cancer ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer ; Cancer metastasis ; Cancer therapies ; Cell Count - methods ; Cell density ; Cell Line, Tumor ; Chemokines ; Disease Models, Animal ; Doxorubicin ; Doxorubicin - analogs & derivatives ; Doxorubicin - pharmacology ; Female ; Immunology ; Inoculation ; Lesions ; Lungs ; Mammary Neoplasms, Experimental - drug therapy ; Mammary Neoplasms, Experimental - pathology ; Medical research ; Medicine and Health Sciences ; Mesentery ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis - drug therapy ; Neoplasm Metastasis - pathology ; Neurosciences ; Pancreas ; Pharmacy ; Polyethylene Glycols - pharmacology ; Potassium ; Research and Analysis Methods ; Rodents ; Tumors
• É parte de: PloS one, 2016-11, Vol.11 (11), p.e0165817-e0165817
• Notas: ObjectType-Article-1
  SourceType-Scholarly Journals-1
  ObjectType-Feature-2
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  Competing Interests: Author Vera Moura (VM) received funding from TREAT U, SA, a commercial company, in the form of salaries. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
  Conceptualization: AG JNM. Data curation: AG. Formal analysis: AG. Funding acquisition: JNM. Investigation: AG. Methodology: AG JNM ML. Project administration: AG JNM. Resources: JNM PF. Supervision: JNM. Validation: AG. Visualization: AG. Writing – original draft: AG. Writing – review & editing: AG JNM NF VM ML SS SD.
  
• Descrição: 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.
  
• Editor: United States: Public Library of Science
  
• Idioma: Inglês