Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer

Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer

The tumor microenvironment is known to play a key role in altering the properties and behavior of nearby cancer cells. Its influence on resistance to endocrine therapy and cancer relapse, however, is poorly understood. Here we investigate the interaction of mammary fibroblasts and estrogen receptor-...

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Main Authors: Holton, Sarah E., Bergamaschi, Anna, Katzenellenbogen, Benita S., Bhargava, Rohit
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016150/
id pubmed-4016150
recordtype oai_dc
spelling pubmed-40161502014-05-14 Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer Holton, Sarah E. Bergamaschi, Anna Katzenellenbogen, Benita S. Bhargava, Rohit Research Article The tumor microenvironment is known to play a key role in altering the properties and behavior of nearby cancer cells. Its influence on resistance to endocrine therapy and cancer relapse, however, is poorly understood. Here we investigate the interaction of mammary fibroblasts and estrogen receptor-positive breast cancer cells in three-dimensional culture models in order to characterize gene expression, cellular changes, and the secreted protein factors involved in the cellular cross-talk. We show that fibroblasts, which are the predominant cell type found in the stroma adjacent to the cancer cells in a tumor, induce an epithelial-to-mesenchymal transition in the cancer cells, leading to hormone-independent growth, a more invasive phenotype, and resistance to endocrine therapy. Here, we applied a label-free chemical imaging modality, Fourier transform infrared (FT-IR) spectroscopic imaging, to identify cells that had transitioned to hormone-independent growth. Both the molecular and chemical profiles identified here were translated from cell culture to patient samples: a secreted protein signature was used to stratify patient populations based on gene expression and FT-IR was used to characterize breast tumor patient biopsies. Our findings underscore the role of mammary fibroblasts in promoting aggressiveness and endocrine therapy resistance in ER-positive breast cancers and highlight the utility of FT-IR for the further characterization of breast cancer samples. Public Library of Science 2014-05-09 /pmc/articles/PMC4016150/ /pubmed/24816718 http://dx.doi.org/10.1371/journal.pone.0096878 Text en © 2014 Holton et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Holton, Sarah E.
Bergamaschi, Anna
Katzenellenbogen, Benita S.
Bhargava, Rohit
spellingShingle Holton, Sarah E.
Bergamaschi, Anna
Katzenellenbogen, Benita S.
Bhargava, Rohit
Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
author_facet Holton, Sarah E.
Bergamaschi, Anna
Katzenellenbogen, Benita S.
Bhargava, Rohit
author_sort Holton, Sarah E.
title Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
title_short Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
title_full Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
title_fullStr Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
title_full_unstemmed Integration of Molecular Profiling and Chemical Imaging to Elucidate Fibroblast-Microenvironment Impact on Cancer Cell Phenotype and Endocrine Resistance in Breast Cancer
title_sort integration of molecular profiling and chemical imaging to elucidate fibroblast-microenvironment impact on cancer cell phenotype and endocrine resistance in breast cancer
description The tumor microenvironment is known to play a key role in altering the properties and behavior of nearby cancer cells. Its influence on resistance to endocrine therapy and cancer relapse, however, is poorly understood. Here we investigate the interaction of mammary fibroblasts and estrogen receptor-positive breast cancer cells in three-dimensional culture models in order to characterize gene expression, cellular changes, and the secreted protein factors involved in the cellular cross-talk. We show that fibroblasts, which are the predominant cell type found in the stroma adjacent to the cancer cells in a tumor, induce an epithelial-to-mesenchymal transition in the cancer cells, leading to hormone-independent growth, a more invasive phenotype, and resistance to endocrine therapy. Here, we applied a label-free chemical imaging modality, Fourier transform infrared (FT-IR) spectroscopic imaging, to identify cells that had transitioned to hormone-independent growth. Both the molecular and chemical profiles identified here were translated from cell culture to patient samples: a secreted protein signature was used to stratify patient populations based on gene expression and FT-IR was used to characterize breast tumor patient biopsies. Our findings underscore the role of mammary fibroblasts in promoting aggressiveness and endocrine therapy resistance in ER-positive breast cancers and highlight the utility of FT-IR for the further characterization of breast cancer samples.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016150/
_version_ 1612087443415105536

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