Microenvironmental independence associated with tumor progression

Alexander R.A. Anderson, Mohamed Hassanein, Kevin M. Branch, Jenny Lu, Nichole A. Lobdell, Julie Maier, David Basanta, Brandy Weidow, Archana Narasanna, Carlos L. Arteaga, Albertb Reynolds, Vito Quaranta, Lourdes Estrada, Alissa M. Weaver

Research output: Contribution to journalArticle

47 Scopus citations

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 discretecontinuum 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.

Original languageEnglish (US)
Pages (from-to)8797-8806
Number of pages10
JournalCancer research
Volume69
Issue number22
DOIs
StatePublished - Nov 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Anderson, A. R. A., Hassanein, M., Branch, K. M., Lu, J., Lobdell, N. A., Maier, J., Basanta, D., Weidow, B., Narasanna, A., Arteaga, C. L., Reynolds, A., Quaranta, V., Estrada, L., & Weaver, A. M. (2009). Microenvironmental independence associated with tumor progression. Cancer research, 69(22), 8797-8806. https://doi.org/10.1158/0008-5472.CAN-09-0437