Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma

Abstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (T...

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Autores principales: Lucas A. Tomko, Ryan C. Hill, Alexander Barrett, Joseph M. Szulczewski, Matthew W. Conklin, Kevin W. Eliceiri, Patricia J. Keely, Kirk C. Hansen, Suzanne M. Ponik
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/23bb514e9fc84cb880e52835f19ae0f8
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spelling oai:doaj.org-article:23bb514e9fc84cb880e52835f19ae0f82021-12-02T15:08:23ZTargeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma10.1038/s41598-018-31126-w2045-2322https://doaj.org/article/23bb514e9fc84cb880e52835f19ae0f82018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31126-whttps://doaj.org/toc/2045-2322Abstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (TACS). Late stages of this progression are characterized by the presence of bundled, straight collagen (TACS-2) that become oriented perpendicular to the tumor-stromal boundary (TACS-3). Importantly, the presence of TACS-3 collagen is an independent predictor of poor patient outcome. At present, it remains unclear whether reorganization of the collagen matrix is the consequence of mechanical or compositional tissue remodeling. Here, we identify compositional changes in ECM correlating to collagen fiber reorganization from nineteen normal and invasive ductal carcinoma (IDC) patient biopsies using matrisome-targeted proteomics. Twenty-seven ECM proteins were significantly altered in IDC samples compared to normal tissue. Further, a set of nineteen matrisome proteins positively correlate and five proteins inversely correlate with IDC tissues containing straightened collagen fibers. Tenascin-C and thrombospondin-2 significantly co-localized with aligned collagen fibers in IDC tissues. This study highlights the compositional change in matrisome proteins accompanying collagen re-organization during breast cancer progression and provides candidate proteins for investigation into cellular and structural influences on collagen alignment.Lucas A. TomkoRyan C. HillAlexander BarrettJoseph M. SzulczewskiMatthew W. ConklinKevin W. EliceiriPatricia J. KeelyKirk C. HansenSuzanne M. PonikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lucas A. Tomko
Ryan C. Hill
Alexander Barrett
Joseph M. Szulczewski
Matthew W. Conklin
Kevin W. Eliceiri
Patricia J. Keely
Kirk C. Hansen
Suzanne M. Ponik
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
description Abstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (TACS). Late stages of this progression are characterized by the presence of bundled, straight collagen (TACS-2) that become oriented perpendicular to the tumor-stromal boundary (TACS-3). Importantly, the presence of TACS-3 collagen is an independent predictor of poor patient outcome. At present, it remains unclear whether reorganization of the collagen matrix is the consequence of mechanical or compositional tissue remodeling. Here, we identify compositional changes in ECM correlating to collagen fiber reorganization from nineteen normal and invasive ductal carcinoma (IDC) patient biopsies using matrisome-targeted proteomics. Twenty-seven ECM proteins were significantly altered in IDC samples compared to normal tissue. Further, a set of nineteen matrisome proteins positively correlate and five proteins inversely correlate with IDC tissues containing straightened collagen fibers. Tenascin-C and thrombospondin-2 significantly co-localized with aligned collagen fibers in IDC tissues. This study highlights the compositional change in matrisome proteins accompanying collagen re-organization during breast cancer progression and provides candidate proteins for investigation into cellular and structural influences on collagen alignment.
format article
author Lucas A. Tomko
Ryan C. Hill
Alexander Barrett
Joseph M. Szulczewski
Matthew W. Conklin
Kevin W. Eliceiri
Patricia J. Keely
Kirk C. Hansen
Suzanne M. Ponik
author_facet Lucas A. Tomko
Ryan C. Hill
Alexander Barrett
Joseph M. Szulczewski
Matthew W. Conklin
Kevin W. Eliceiri
Patricia J. Keely
Kirk C. Hansen
Suzanne M. Ponik
author_sort Lucas A. Tomko
title Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
title_short Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
title_full Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
title_fullStr Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
title_full_unstemmed Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
title_sort targeted matrisome analysis identifies thrombospondin-2 and tenascin-c in aligned collagen stroma from invasive breast carcinoma
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/23bb514e9fc84cb880e52835f19ae0f8
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