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

McCart Reed, Amy E., Song, Sarah, Kutasovic, Jamie R., Reid, Lynne E., Valle, Jordan M., Vargas, Ana Cristina, Smart, Chanel E. and Simpson, Peter T. (2013) Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer. Virchows Archiv, 463 4: 535-545. doi:10.1007/s00428-013-1468-3


Author McCart Reed, Amy E.
Song, Sarah
Kutasovic, Jamie R.
Reid, Lynne E.
Valle, Jordan M.
Vargas, Ana Cristina
Smart, Chanel E.
Simpson, Peter T.
Title Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer
Journal name Virchows Archiv   Check publisher's open access policy
ISSN 0945-6317
1432-2307
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1007/s00428-013-1468-3
Volume 463
Issue 4
Start page 535
End page 545
Total pages 11
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2014
Language eng
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.
Keyword Thrombospondin-4
Breast cancer
Extracellular matrix
Cancer-associated stroma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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