Arig Ibrahim-Hashim1,2,3, Kimberly Luddy1,2,4, Dominique Abrahams1,2, Pedro Enriquez-Navas1,2, Sultan Damgaci2, Jiqiang Yao5, Tingan Chen6, Marilyn M Bui6,7, Robert J Gillies1,2,8, Cliona O'Farrelly4, Christina L Richards3, Joel S Brown1,3,9,10, Robert A Gatenby11,12,13. 1. Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 2. Department of Cancer Physiology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 3. Department of Integrative Biology, University of South Florida, Tampa, FL, USA. 4. School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. 5. Department of Biostatistics & Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 6. Analytic Microscopy Core, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 7. Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 8. Department of Radiology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 9. Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. 10. Department of Biological Sciences, University of Illinois, at Chicago, Chicago, IL, USA. 11. Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA. robert.gatenby@moffitt.org. 12. Department of Radiology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. robert.gatenby@moffitt.org. 13. Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA. robert.gatenby@moffitt.org.
Abstract
BACKGROUND: Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation. METHODS: We investigate this "evolutionary arms race" through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round. RESULTS: The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice. CONCLUSION: Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.
BACKGROUND:Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation. METHODS: We investigate this "evolutionary arms race" through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mousecarcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round. RESULTS: The evolved SCIDmice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCIDmice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice. CONCLUSION: Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.
Authors: R N Van Gelder; M E von Zastrow; A Yool; W C Dement; J D Barchas; J H Eberwine Journal: Proc Natl Acad Sci U S A Date: 1990-03 Impact factor: 11.205
Authors: Arig Ibrahim-Hashim; Mark Robertson-Tessi; Pedro M Enriquez-Navas; Mehdi Damaghi; Yoganand Balagurunathan; Jonathan W Wojtkowiak; Shonagh Russell; Kam Yoonseok; Mark C Lloyd; Marilyn M Bui; Joel S Brown; Alexander R A Anderson; Robert J Gillies; Robert A Gatenby Journal: Cancer Res Date: 2017-03-01 Impact factor: 12.701
Authors: Ian F Robey; Brenda K Baggett; Nathaniel D Kirkpatrick; Denise J Roe; Julie Dosescu; Bonnie F Sloane; Arig Ibrahim Hashim; David L Morse; Natarajan Raghunand; Robert A Gatenby; Robert J Gillies Journal: Cancer Res Date: 2009-03-10 Impact factor: 12.701
Authors: Mariano Alvarez; Julie Ferreira de Carvalho; Armel Salmon; Malika L Ainouche; Armand Cavé-Radet; Abdelhak El Amrani; Tammy E Foster; Sydney Moyer; Christina L Richards Journal: Mol Ecol Date: 2018-06-22 Impact factor: 6.185
Authors: Vincenzo Gervasi; Erlend B Nilsen; Håkan Sand; Manuela Panzacchi; Geir R Rauset; Hans C Pedersen; Jonas Kindberg; Petter Wabakken; Barbara Zimmermann; John Odden; Olof Liberg; Jon E Swenson; John D C Linnell Journal: J Anim Ecol Date: 2011-11-11 Impact factor: 5.091