title: Microenvironmental independence associated with tumor progression.
abstract: Tumor-microenvironment interactions are increasingly recognized to influence tumor progression. To understand the competitive dynamics of tumor cells in diverse microenvironments, we experimentally parameterized a hybrid discrete-continuum mathematical model with phenotypic trait data from a set of related mammary cell lines with normal, transformed, or tumorigenic properties. Surprisingly, in a resource-rich microenvironment, with few limitations on proliferation or migration, transformed (but not tumorigenic) cells were most successful and outcompeted other cell types in heterogeneous tumor simulations. Conversely, constrained microenvironments with limitations on space and/or growth factors gave a selective advantage to phenotypes derived from tumorigenic cell lines. Analysis of the relative performance of each phenotype in constrained versus unconstrained microenvironments revealed that, although all cell types grew more slowly in resource-constrained microenvironments, the most aggressive cells were least affected by microenvironmental constraints. A game theory model testing the relationship between microenvironment resource availability and competitive cellular dynamics supports the concept that microenvironmental independence is an advantageous cellular trait in resource-limited microenvironments.
authors.affiliation: Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, Florida FL 33629, USA. alexander.anderson@moffitt.org
authors.forename: Alexander R A
authors.initials: AR
authors.lastname: Anderson
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hassanein
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Branch
authors.forename: Jenny
authors.initials: J
authors.lastname: Lu
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Lobdell
authors.forename: Julie
authors.initials: J
authors.lastname: Maier
authors.forename: David
authors.initials: D
authors.lastname: Basanta
authors.forename: Brandy
authors.initials: B
authors.lastname: Weidow
authors.forename: Archana
authors.initials: A
authors.lastname: Narasanna
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.forename: Vito
authors.initials: V
authors.lastname: Quaranta
authors.forename: Lourdes
authors.initials: L
authors.lastname: Estrada
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Weaver
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005716:Game Theory; D006801:Humans; D008962:Models, Theoretical