Modeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature

Kerri Ann Norton, Kideok Jin, Aleksander S. Popel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates.

Original languageEnglish (US)
Pages (from-to)56-68
Number of pages13
JournalJournal of Theoretical Biology
Volume452
DOIs
StatePublished - Sep 7 2018

Keywords

  • Angiogenesis
  • Cancer stem cells
  • Hypoxia
  • Immune cells
  • Microenvironment
  • Tumor

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics

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