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

Journal of Theoretical Biology
Kerri-Ann NortonAleksander S Popel

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...Continue Reading

Citations

Feb 5, 2019·JCO Clinical Cancer Informatics·John MetzcarPaul Macklin
Jan 23, 2019·Frontiers in Oncology·Chang GongAleksander S Popel
Feb 1, 2019·Processes·Kerri-Ann NortonAleksander S Popel
May 8, 2019·Breast Cancer Research : BCR·Olivia K Provance, Joan Lewis-Wambi
Nov 13, 2020·Cancer Immunology, Immunotherapy : CII·Louis T CurtisHermann B Frieboes
Dec 29, 2020·PLoS Computational Biology·Colin G Cess, Stacey D Finley
Nov 20, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Tuli Dey
Mar 6, 2019·Journal of Theoretical Biology·Grace E MahlbacherHermann B Frieboes
Apr 6, 2021·Frontiers in Endocrinology·Ximena M Bustamante-MarinDelisha A Stewart
Dec 11, 2021·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Min Song, Stacey D Finley
Jan 1, 2022·WIREs Mechanisms of Disease·Yu ZhangAleksander S Popel

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