Tumor-associated macrophages and stromal TNF-α regulate collagen structure in a breast tumor model as visualized by second harmonic generation

Ryan M. Burke; Kelley S. Madden; Seth W. Perry; Martha L. Zettel; Edward B. Brown III

doi:10.1117/1.JBO.18.8.086003

2 August 2013 Tumor-associated macrophages and stromal TNF-α regulate collagen structure in a breast tumor model as visualized by second harmonic generation

Ryan M. Burke, Kelley S. Madden, Seth W. Perry, Martha L. Zettel, Edward B. Brown III

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Journal of Biomedical Optics, Vol. 18, Issue 8, 086003 (August 2013). https://doi.org/10.1117/1.JBO.18.8.086003

Abstract

Collagen fibers can be imaged with second harmonic generation (SHG) and are associated with efficient tumor cell locomotion. Preferential locomotion along these fibers correlates with a more aggressively metastatic phenotype, and changes in SHG emission properties accompany changes in metastatic outcome. We therefore attempted to elucidate the cellular and molecular machinery that influences SHG in order to understand how the microstructure of tumor collagen fibers is regulated. By quantifying SHG and immunofluorescence (IF) from tumors grown in mice with and without stromal tumor necrosis factor (TNF)-α and in the presence or absence of tumor-associated macrophages (TAMs), we determined that depletion of TAMs alters tumor collagen fibrillar microstructure as quantified by SHG and IF. Furthermore, we determined that abrogation of TNF-α expression by tumor stromal cells also alters fibrillar microstructure and that subsequent depletion of TAMs has no further effect. In each case, metastatic burden correlated with optical readouts of collagen microstructure. Our results implicate TAMs and stromal TNF-α as regulators of breast tumor collagen microstructure and suggest that this regulation plays a role in tumor metastasis. Furthermore, these results indicate that quantification of SHG represents a useful strategy for evaluating the cells and molecular pathways responsible for manipulating fibrillar collagen in breast tumor models.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Ryan M. Burke, Kelley S. Madden, Seth W. Perry, Martha L. Zettel, and Edward B. Brown III "Tumor-associated macrophages and stromal TNF-α regulate collagen structure in a breast tumor model as visualized by second harmonic generation," Journal of Biomedical Optics 18(8), 086003 (2 August 2013). https://doi.org/10.1117/1.JBO.18.8.086003

Published: 2 August 2013

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