Metastatic cells exploit their stoichiometric niche in the network of cancer ecosystems
Menée à partir de données vasculaires, physiologiques ou stoechiométriques portant sur 28 types tissulaires, cette étude examine le mécanisme par lequel des cellules cancéreuses issues d'un organe donné vont coloniser spécifiquement certains organes
Metastasis is a nonrandom process with varying degrees of organotropism—specific source-acceptor seeding. Understanding how patterns between source and acceptor tumors emerge remains a challenge in oncology. We hypothesize that organotropism results from the macronutrient niche of cells in source and acceptor organs. To test this, we constructed and analyzed a metastatic network based on 9303 records across 28 tissue types. We found that the topology of the network is nested and modular with scale-free degree distributions, reflecting organotropism along a specificity/generality continuum. The variation in topology is significantly explained by the matching of metastatic cells to their stoichiometric niche. Specifically, successful metastases are associated with higher phosphorus content in the acceptor compared to the source organ, due to metabolic constraints in proliferation crucial to the invasion of new tissues. We conclude that metastases are codetermined by processes at source and acceptor organs, where phosphorus content is a limiting factor orchestrating tumor ecology. The ecology of metastasis organotropically structured based on phosphorous availability.
Science Advances , article en libre accès, 2022