Imagable 4T1 model for the study of late stage breast cancer

Kai Tao; Min Fang; Joseph Alroy; G Gary Sahagian

doi:10.1186/1471-2407-8-228

journal article Aug 09, 2008

Imagable 4T1 model for the study of late stage breast cancer

Kai Tao

Min Fang

Joseph Alroy G Gary Sahagian

BMC Cancer Vol. 8 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1186/1471-2407-8-228

Abstract

AbstractBackgroundThe 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene functionin vivo. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported.MethodsThe lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cellsin vivo. Biophotonic imaging was used to characterize growth and metastasis of the linesin vivoand an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed.ResultsGrowth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified.ConclusionThe production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously appreciated in orchestrating changes in the tumor environment conducive to tumor cell dissemination and metastasis. The new cell lines will greatly facilitate the study of late stage breast and preclinical assessment of cancer drugs and other therapeutics particularly those targeting immune system effects on tumor metastasis.

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Published: Aug 09, 2008
Vol/Issue: 8(1)
License: View

Authors

Purple Mountain Observatory, Chinese Academy of Sciences, 10 Yuanhua Road, Nanjing 210023, China

Cite This Article

Kai Tao, Min Fang, Joseph Alroy, et al. (2008). Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer, 8(1). https://doi.org/10.1186/1471-2407-8-228

Imagable 4T1 model for the study of late stage breast cancer

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