4T1 Metastatic Breast Cancer Model

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Overview:

The 4T1 metastatic breast cancer model is a syngeneic xenograft model based on 4T1-12B, a luciferase-expressing clone of the well characterized 4T1 mouse mammary tumor cell line (1-4).  The luciferase-expressing line can be introduced orthotopically into the mammary fat pad of nude, scid or normal BALB/c mice by surgery or direct injection, intravenously by tail vein injection, or arterially by surgical catheterization of the right carotid artery. When introduced orthotopically, the 4T1 line grows rapidly at the primary site and forms metastases in lungs, liver, bone and brain over a period of 3-6 weeks. When introduced via the tail vein or arterially, metastases are apparent in these same organs after 1-2 weeks. The rapid and efficient metastasis to organs affected in human breast cancer makes the 4T1 model an excellent mouse model for the study of metastatic progression of breast cancer in humans. Because the model is syngeneic in BALB/c mice, it can be used to study the role of the immune system in tumor growth and metastasis.

Advantages of 4T1 Model:

  • Syngeneic breast cancer model - the 4T1 cell line was derived from a spontaneously arising BALB/c mammary tumor (1)
  • Metastatic properties extensively characterized (1,4)
  • Availability of genetically-related sibling cell lines (1)
  • Efficient, reproducible metastasis to lungs, liver, bone and brain (1,4)
  • Highly physiological mouse model that closely resembles breast cancer in humans (1,4)
  • Problems associated with using human tumor cell lines in mice (e.g., slow growth, inefficient metastasis, etc.) are eliminated
  • Gene expression profiles of 4T1 and sibling cell lines have been reported (2,4)

Applications:

  • Investigation of the basis for metastasis to lungs, liver, bone and brain
  • Analysis of gene function in tumor growth and metastasis
  • Determination of immune system effects on tumor growth and metastasis
  • Determination of the effects of drugs and therapeutic procedures on breast tumor growth and metastasis
  • Drug efficacy and toxicity studies

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Kinetics of tumor growth and metastasis of luciferase-expressing 4T1 cell line in syngeneic BALB/c mice. The top panel shows images of two mice obtained at 1-week intervals (from left to right) after orthotopic injection of the 106 cells in the no. 4 mammary fat pad. Note biphasic growth of the primary tumor and metastasis to the thoracic region beginning at 3-4 weeks. Imaging of organs removed from the two animals after 6 weeks (bottom panels) reveals metastasis to lungs, liver, bone and brain.

Pathology:

Primary tumor (in mammary fat pad)
Metastases in lung
Metastasis in liver
Metastasis in bone

Related cell lines available for use by facility users:

4T1-L1-c12b - a luciferae-expressing 4T1-luc12B clone isolated from lung metastases. The line displays mesenchymal characteristics and a higher rate of metastasis to lung relative to the parental 4T1-luc12B line (5).

4T1 Cell Pools isolated from bone, brain, liver and lungs after several rounds of in vivo growth and metastasis. These pools metastasize more effectively to the organs from which they were  isolated.

66c14-luc - a luciferase-expressing clone of 66c14, a 4T1 sibling cell line isolated from the same tumor as 4T1 (3). 66c14 and 66c14-luc are tumorigenic lines that metastasize weakly to lungs.

References:

1. Aslakson CJ, Miller FR., "Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor." Cancer Res. 1992 Mar 15;52(6):1399-405.

2. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA., "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis." Cell. 2004 Jun 25;117(7):927-39.

3. Li J, Sahagian GG. "Demonstration of tumor suppression by Man-6-P/IGF-2 Receptor." Oncogene 2004; 23:9359-68.

4. Tao K, Alroy J, Sahagian GG. "Imagable 4T1 model for the study of late stage breast cancer.", BMC Cancer 2008; 8:228.