Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties

Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties Federica Eduati, Maisa van Genderen, Jeroen Kneppers, Anniek Zaalberg, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3265572/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Feb, 2024 Read the published version in npj Systems Biology and Applications → Version 1 posted 11 You are reading this latest preprint version Abstract Inhibiting androgen receptor (AR) signaling through androgen deprivation therapy (ADT) reduces prostate cancer (PCa) growth in virtually all patients, but response is temporary, and resistance inevitably develops, ultimately leading to lethal castration-resistant prostate cancer (CRPC). The tumor microenvironment (TME) plays an important role in the development and progression of PCa. In addition to tumor cells, TME-resident macrophages and fibroblasts express AR and are therefore also affected by ADT. However, the interplay of different TME cell types in the development of CRPC remains largely unexplored. To understand the complex stochastic nature of cell-cell interactions, we created a PCa-specific agent-based model (PCABM) based on in vitro cell proliferation data. PCa cells, fibroblasts, “pro-inflammatory” M1-like and “pro-tumor” M2-like polarized macrophages are modeled as agents from a simple set of validated base assumptions. PCABM allows us to simulate the effect of ADT on the interplay between various prostate TME cell types. The resulting in vitro growth patterns mimic human PCa. Our PCABM can effectively model hormonal perturbations by ADT, in which PCABM suggests that CRPC arises in clusters of resistant cells, as is observed in multifocal PCa. In addition, fibroblasts compete for cellular space in the TME while simultaneously creating niches for tumor cells to proliferate in. Finally, PCABM predicts that ADT has immunomodulatory effects on macrophages that may enhance tumor survival. Taken together, these results suggest that AR plays a critical role in the cellular interplay and stochastic interactions in the TME that influence tumor cell behavior and CRPC development. Biological sciences/Cancer Biological sciences/Systems biology Health sciences/Oncology agent-based modeling androgen receptor tumor microenvironment androgen deprivation therapy castration resistance Full Text Additional Declarations (Not answered) Supplementary Files vanGenderenatalSupplfigs.pdf vanGenderenatalSuppltable1.xlsx vanGenderenatalSuppltable2.xlsx Cite Share Download PDF Status: Published Journal Publication published 21 Feb, 2024 Read the published version in npj Systems Biology and Applications → Version 1 posted Editorial decision: revise 11 Sep, 2023 Review # 3 received at journal 08 Sep, 2023 Reviewer # 3 agreed at journal 08 Sep, 2023 Review # 2 received at journal 08 Sep, 2023 Reviewer # 2 agreed at journal 08 Sep, 2023 Review # 1 received at journal 28 Aug, 2023 Reviewer # 1 agreed at journal 28 Aug, 2023 Reviewers invited by journal 23 Aug, 2023 Submission checks completed at journal 16 Aug, 2023 Editor assigned by journal 15 Aug, 2023 First submitted to journal 15 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3265572","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":229405171,"identity":"0896bde2-e14a-41ac-9154-be279bf3d7c6","order_by":0,"name":"Federica 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