Abstract
Immunodeficient mice are widely used for cancer research as they can provide an in vivo system in which to study the tumorigenicity and metastatic potential of human cancer cells. The athymic or “nude” mouse has been employed for a variety of experimental analyses of tumor growth, invasion, and metastasis. This chapter describes two types of experimental design for studying metastasis in vivo. The spontaneous metastasis models assess the ability of cells to disseminate from a local tumor, and are commonly initiated by the injection of the cells into an organ reflecting the tissue of origin of the cancer (orthotopic injection). Models of experimental metastasis evaluate the ability of tumor cells to arrest, extravasate, and grow in various organs following intravascular injection. The appropriate design of animal models using nude mice, and established human tumor cell lines, assists in the generation of novel information about the metastatic phenotype, and provides a valuable, preclinical system for testing anti-metastatic therapies.
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References
Fidler IJ (2002) Critical determinants of metastasis. Semin Cancer Biol 12:89–96
Xie H, Turner T, Wang MH, Singh RK, Siegal GP, Wells A (1995) In vitro invasiveness of DU-145 human prostate carcinoma cells is modulated by EGF receptor-mediated signals. Clin Exp Metastasis 13:407–419
Li L, Price JE, Fan D, Zhang RD, Bucana CD, Fidler IJ (1989) Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites. J Natl Cancer Inst 81:1406–1412
Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793–804
Price JE (1996) Metastasis from human breast cancer cell lines. Breast Cancer Res Treat 39:93–102
Bankert RB, Hess SD, Egilmez NK (2002) SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions. Front Biosci 7:c44–c62
Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ (1999) In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1:50–62
Cespedes MV, Espina C, Garcia-Cabezas MA, Trias M, Boluda A, Gomez del Pulgar MT, Sancho FJ, Nistal M, Lacal JC, Mangues R (2007) Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol 170:1077–1085
Chelouche Lev D, Kiriakova G, Price JE (2003) Selection of more aggressive variants of the GI101A human breast cancer cell line: a model for analyzing the metastatic phenotype of breast cancer. Clin Exp Metastasis 20:515–523
Contag CH, Jenkins D, Contag PR, Negrin RS (2000) Use of reporter genes for optical measurements of neoplastic disease in vivo. Neoplasia 2:41–52
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo G, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549
Arumugam T, Ramachandran V, Logsdon CD (2006) Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models. J Natl Cancer Inst 98:1806–1818
Price JE, Daniels LM, Campbell DE, Giavazzi R (1989) Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice. Clin Exp Metastasis 7:55–68
Yoneda T, Williams PJ, Hiraga T, Niewolna M, Nishimura R (2001) A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro. J Bone Miner Res 16:1486–1495
Kim LS, Huang S, Lu W, Chelouche Lev D, Price JE (2004) Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Clin Exp Metastasis 21:107–118
Villares GJ, Zigler M, Wang H, Melnikova VO, Wu H, Friedman R, Leslie MC, Vivas-Mejia P, Lopez-Berestein G, Sood AK, Bar-Eli M (2008) Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res 68:9078–9086
Koura AN, Liu W, Kitadai Y, Singh RK, Radinsky R, Ellis LM (1996) Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by cell density. Cancer Res 56:3891–3894
Welch DR (1997) Technical considerations for studying cancer metastasis in vivo. Clin Exp Metastasis 15:272–306
Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806
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Price, J.E. (2014). Spontaneous and Experimental Metastasis Models: Nude Mice. In: Dwek, M., Schumacher, U., Brooks, S. (eds) Metastasis Research Protocols. Methods in Molecular Biology, vol 1070. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8244-4_17
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DOI: https://doi.org/10.1007/978-1-4614-8244-4_17
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