Abstract
In many tumor types, only a minor pool of cancer cells—the so-called cancer stem cells—is able to colonize distant organs and give rise to secondary tumors. In humans, the liver is one of the main target organs for many metastatic tumor types, including colorectal cancer. However, mouse tumour models only rarely spontaneously metastasize to the liver. Therefore, reliable in vivo experimental metastasis assays are crucial to study cell seeding capacity and the mechanisms controlling these metastatic stem cell properties. Here, we describe an intrasplenic injection model that mimics the process of liver metastasis occurring in cancer patients.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Fico F, Bousquenaud M, Ruegg C, Santamaria-Martinez A (2019) Breast cancer stem cells with tumor—versus metastasis-initiating capacities are modulated by TGFBR1 inhibition. Stem Cell Reports 13(1):1–9. https://doi.org/10.1016/j.stemcr.2019.05.026
Oskarsson T, Batlle E, Massague J (2014) Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell 14(3):306–321. https://doi.org/10.1016/j.stem.2014.02.002
Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J (2012) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481(7379):85–89. https://doi.org/10.1038/nature10694
Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC (2010) A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6(6):603–615. https://doi.org/10.1016/j.stem.2010.04.001
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323. https://doi.org/10.1016/j.stem.2007.06.002
Oskarsson T, Acharyya S, Zhang XH, Vanharanta S, Tavazoie SF, Morris PG, Downey RJ, Manova-Todorova K, Brogi E, Massague J (2011) Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 17(7):867–874. https://doi.org/10.1038/nm.2379nm.2379
Ordonez-Moran P, Dafflon C, Imajo M, Nishida E, Huelsken J (2015) HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer. Cancer Cell 28(6):815–829. https://doi.org/10.1016/j.ccell.2015.11.001
Chowdhury S, Ongchin M, Sharratt E, Dominguez I, Wang J, Brattain MG, Rajput A (2013) Intra-tumoral heterogeneity in metastatic potential and survival signaling between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines. PLoS One 8(4):e60299. https://doi.org/10.1371/journal.pone.0060299
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115. https://doi.org/10.1038/nature05384
O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110. https://doi.org/10.1038/nature05372
Acknowledgments
A.S.-M. was supported by an SNSF Ambizione career award (PZ00P3_154751), and P.O-M was supported by the University of Nottingham. This protocol was developed in the Huelsken’s lab, so we would like to thank past and current members of this lab for their help in developing this method, specially to Prof. Joerg Huelsken.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Dafflon, C., Santamaría-Martínez, A., Ordóñez-Morán, P. (2020). An Intrasplenic Injection Model for the Study of Cancer Stem Cell Seeding Capacity. In: Ordóñez-Morán, P. (eds) Intestinal Stem Cells. Methods in Molecular Biology, vol 2171. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0747-3_20
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0747-3_20
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0746-6
Online ISBN: 978-1-0716-0747-3
eBook Packages: Springer Protocols