Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent and nature of these interactions remain largely unknown. We postulated that tumors develop ecological interactions that sustain diversity and facilitate metastasis. Using a combination of fluorescent barcoding, mathematical modeling, metabolic analysis, and in vivo models, we show that the Allee effect, i.e., growth dependency on population size, is a feature of tumor lineages and that cooperative ecological interactions between lineages alleviate the Allee barriers to growth in a model of triple-negative breast cancer. Soluble metabolite exchange formed the basis for these cooperative interactions and catalyzed the establishment of a polyclonal community that displayed enhanced metastatic dissemination and outgrowth in xenograft models. Our results highlight interclonal metabolite exchange as a key modulator of tumor ecology and a contributing factor to overcoming Allee effect-associated growth barriers to metastasis.

Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect / B.J. Hershey, S. Barozzi, F. Orsenigo, S. Pompei, F. Iannelli, S. Kamrad, V. Matafora, F. Pisati, L. Calabrese, G. Fragale, G. Salvadori, E. Martini, M.G. Totaro, S. Magni, R. Guan, D. Parazzoli, P. Maiuri, A. Bachi, K.R. Patil, M. Cosentino Lagomarsino, K.M. Havas. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 9:37(2023 Sep 15), pp. eadh4184.1-eadh4184.18. [10.1126/sciadv.adh4184]

Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect

F. Iannelli;F. Pisati;G. Fragale;G. Salvadori;E. Martini;M.G. Totaro;M. Cosentino Lagomarsino
Penultimo
;
2023

Abstract

Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent and nature of these interactions remain largely unknown. We postulated that tumors develop ecological interactions that sustain diversity and facilitate metastasis. Using a combination of fluorescent barcoding, mathematical modeling, metabolic analysis, and in vivo models, we show that the Allee effect, i.e., growth dependency on population size, is a feature of tumor lineages and that cooperative ecological interactions between lineages alleviate the Allee barriers to growth in a model of triple-negative breast cancer. Soluble metabolite exchange formed the basis for these cooperative interactions and catalyzed the establishment of a polyclonal community that displayed enhanced metastatic dissemination and outgrowth in xenograft models. Our results highlight interclonal metabolite exchange as a key modulator of tumor ecology and a contributing factor to overcoming Allee effect-associated growth barriers to metastasis.
Settore BIO/11 - Biologia Molecolare
Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
15-set-2023
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1027685
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