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Paracrine behaviors arbitrate parasite-like interactions between tumor subclones

Noble, R. ORCID: 0000-0002-8057-4252, Walther, V., Roumestand, C. , Hochberg, M. E., Hibner, U. & Lassus, P. (2021). Paracrine behaviors arbitrate parasite-like interactions between tumor subclones. Frontiers Ecology and Evolution, 9, 675638.. doi: 10.3389/fevo.2021.675638


Explaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactions in vitro. Surprisingly, we found that, compared to monoculture, growth of the ‘winner’ was enhanced by the presence of the ‘loser’ cell line, whereas growth of the latter was reduced. Mathematical modeling and laboratory assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively ‘farming’ the loser. Our findings add a new level of complexity to the mechanisms underlying subclonal growth dynamics.

Publication Type: Article
Additional Information: © 2021 Noble, Walther, Roumestand, Hochberg, Hibner and Lassus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher Keywords: cancer evolution, intratumor clonal heterogeneity, evolutionary game theory, Parasitism, paracrine signaling, Beta-hydroxybutirate, Lactate, Lotka - Volterra model
Subjects: Q Science > QA Mathematics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments: School of Science & Technology > Mathematics
Text - Published Version
Available under License Creative Commons Attribution.

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Text - Accepted Version
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