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01-10-2013 | Original Article

Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer

Authors: Amy E. McCart Reed, Sarah Song, Jamie R. Kutasovic, Lynne E. Reid, Jordan M. Valle, Ana Cristina Vargas, Chanel E. Smart, Peter T. Simpson

Published in: Virchows Archiv | Issue 4/2013

Abstract

The thromobospondins are a family of extracellular glycoproteins that are activated during tissue remodeling processes such as embryogenesis, wound healing and cancer. Thrombospondin-4 (THBS4) is known to have roles in cellular migration, adhesion and attachment, as well as proliferation in different contexts. Data to support a role in cancer biology is increasing, including for gastrointestinal and prostate tumours. Here, using a combination of immunohistochemistry, immunofluorescence and analysis of publicly available genomic and expression data, we present the first study describing the pattern of expression of THBS4 in normal breast and breast cancer. THBS4 was located to the basement membrane of large ducts and vessels in normal breast tissue, but was absent from epithelium and extracellular matrix. There was a significant induction in expression in cancer-associated stroma relative to normal stroma (P = 0.0033), neoplastic epithelium (P < 0.0001) and normal epithelium (P < 0.0001). There was no difference in stromal expression of THBS4 between invasive ductal carcinomas (IDC) and invasive lobular carcinomas (ILC). The THBS4 mRNA levels were variable yet were generally highest in tumours typically rich in stromal content (ILC, ER positive low grade IDC; luminal A and normal-like subtypes). Genomic alterations of the THBS4 gene (somatic mutations and gene copy number) are rare suggesting this dramatic activation in expression is most likely dynamically regulated through the interaction between invading tumour cells and stromal fibroblasts in the local microenvironment. In summary, THBS4 expression in breast cancer-associated extracellular matrix contributes to the activated stromal response exhibited during tumour progression and this may facilitate invasion of tumour cells.

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Title: Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer
Authors: Amy E. McCart Reed
Sarah Song
Jamie R. Kutasovic
Lynne E. Reid
Jordan M. Valle
Ana Cristina Vargas
Chanel E. Smart
Peter T. Simpson
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 4/2013
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-013-1468-3

At a glance: The STEP trials

Springer Medicine

Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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