Abstract
Metastatic latency is a major concern in the clinic, yet how these disseminated cancer cells survive and initiate metastases is unknown (Massagué and Obenauf, Nature 529:298–306, 2016). Here, we describe an approach to isolate latency competent cancer (LCC) cells from early stage human lung and breast carcinoma cell lines using mouse xenograft models (Malladi, Cell 165:45–60, 2016). Cancer cell lines labeled with GFP-luciferase and antibiotic selection markers were injected intracardially into athymic mice. Three months, post-injection, LCC cells were identified in situ and isolated. Upon reinjection, LCC cells retain their tumorigenic potential, enter a slow-cycling or quiescent state, and evade NK cell-mediated innate immune surveillance.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Massagué J, Obenauf AC (2016) Metastatic colonization. Nature 529(7586):298–306
Malladi S et al (2016) Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165(1):45–60
Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563
Sosa MS, Bragado P, Aguirre-Ghiso JA (2014) Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer 14(9):611–622
Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239–252
Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21(2):137–148
Eyles J et al (2010) Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest 120(6):2030–2039
Kitamura T, Qian B-Z, Pollard JW (2015) Immune cell promotion of metastasis. Nat Rev Immunol 15(2):73–86
Francia G et al (2011) Mouse models of advanced spontaneous metastasis for experimental therapeutics. Nat Rev Cancer 11(2):135–141
Day C-P, Merlino G, Van Dyke T (2015) Preclinical mouse cancer models: a maze of opportunities and challenges. Cell 163(1):39–53
Saxena M, Christofori G (2013) Rebuilding cancer metastasis in the mouse. Mol Oncol 7(2):283–296
Bos PD, Nguyen DX, Massagué J (2010) Modeling metastasis in the mouse. Curr Opin Pharmacol 10(5):571–577
Pelleitier M, Montplaisir S (1975) The nude mouse: a model of deficient T-cell function. Methods Achiev Exp Pathol 7:149–166
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Nair, V.R., Malladi, S. (2019). Mouse Models to Study Natural Killer Cell-Mediated Immunosurveillance and Metastatic Latency. In: López-Soto, A., Folgueras, A. (eds) Cancer Immunosurveillance. Methods in Molecular Biology, vol 1884. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8885-3_9
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8885-3_9
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8884-6
Online ISBN: 978-1-4939-8885-3
eBook Packages: Springer Protocols