Abstract
Metastasis is a complex process that has been historically difficult to model in culture. Host immune responses play critical roles in restraining and promoting metastatic tumor cells. Here we describe a method of 3D organotypic co-culture of natural killer cells and tumor organoids to capture interactions between the two cellular populations. These assays can be used to model key aspects of metastatic biology and to screen for the effectiveness of agents that stimulate natural killer cell cytotoxicity.
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References
Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168(4):670–691
Esposito M, Ganesan S, Kang Y (2021) Emerging strategies for treating metastasis. Nat Cancer 2(3):258–270
Roarty K, Echeverria GV (2021) Laboratory models for investigating breast cancer therapy resistance and metastasis. Front Oncol 11:645698
Cheung KJ, Gabrielson E, Werb Z, Ewald AJ (2013) Collective invasion in breast cancer requires a conserved basal epithelial program. Cell 155(7):1639–1651
Cheung KJ, Padmanaban V, Silvestri V, Schipper K, Cohen JD, Fairchild AN et al (2016) Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc Natl Acad Sci U S A 113(7):E854–E863
Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC et al (2012) ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc Natl Acad Sci U S A 109(39):E2595–E2604
Padmanaban V, Krol I, Suhail Y, Szczerba BM, Aceto N, Bader JS et al (2019) E-cadherin is required for metastasis in multiple models of breast cancer. Nature 573(7774):439–444
Lopez-Soto A, Gonzalez S, Smyth MJ, Galluzzi L (2017) Control of metastasis by NK cells. Cancer Cell 32(2):135–154
Chan IS, Knútsdóttir H, Ramakrishnan G, Padmanaban V, Warrier M, Ramirez JC et al (2020) Cancer cells educate natural killer cells to a metastasis-promoting cell state. J Cell Biol 219(9):e202001134
Wagner J, Pfannenstiel V, Waldmann A, Bergs JWJ, Brill B, Huenecke S et al (2017) A two-phase expansion protocol combining interleukin (IL)-15 and IL-21 improves natural killer cell proliferation and cytotoxicity against rhabdomyosarcoma. Front Immunol 8:676
Loyon R, Picard E, Mauvais O, Queiroz L, Mougey V, Pallandre JR et al (2016) IL-21-induced MHC class II+ NK cells promote the expansion of human uncommitted CD4+ central memory T cells in a macrophage migration inhibitory factor-dependent manner. J Immunol 197(1):85–96
Zahavi D, AlDeghaither D, O’Connell A, Weiner LM (2018) Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy. Antib Ther 1(1):7–12
Acknowledgments
The authors thank J. McCann for constructive comments on the manuscript. A.J.E. received support for this project through grants from: the Breast Cancer Research Foundation (BCRF-20-048), Twisted Pink Foundation, Hope Scarves, the Jayne Koskinas Ted Giovanis Foundation, and the National Institutes of Health/National Cancer Institute (U01CA217846, U54CA2101732, 3P30CA006973). I.S.C. received support for this project through grants from: National Institutes of Health/National Cancer Institute (T32CA009071) and the Conquer Cancer Foundation Young Investigator Award. A.J.E. has unlicensed patents and patent applications on the use of 3D culture assays to identify invasive cancer cell populations, on the use of antibodies as anti-cancer therapeutics, and on NK cell-cancer cell co-cultures (w/ I.S.C.). A.J.E.’s spouse is an employee of Immunocore.
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Chan, I.S., Ewald, A.J. (2022). Organoid Co-culture Methods to Capture Cancer Cell–Natural Killer Cell Interactions. In: Shimasaki, N. (eds) Natural Killer (NK) Cells. Methods in Molecular Biology, vol 2463. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2160-8_17
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DOI: https://doi.org/10.1007/978-1-0716-2160-8_17
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Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2159-2
Online ISBN: 978-1-0716-2160-8
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