Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression

BMC Cancer

Helen C Plant³  Abhishek S Kashyap³  Kerry J Manton³  Brett G Hollier³  Cameron P Hurst²  Sandra R Stein⁴  Glenn D Francis⁴  Geoffrey F Beadle¹  Zee Upton³  David I Leavesley³ 

[1] Royal Brisbane and Women’s Hospital, Brisbane, Australia

[2] Academic Clinical Research Office, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

[3] Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

[4] Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia

关键词: Vitronectin;    Metastasis;    Insulin-like growth factor;    Extracellular matrix;    Breast cancer;    Biomarker;   

Others  :  1121265
DOI  :  10.1186/1471-2407-14-627

 received in 2013-09-19, accepted in 2014-08-21,  发布年份 2014

【 摘 要 】

Background

Cancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I: IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays.

Methods

Semiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples.

Results

The IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while β₁ integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and β₁ integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression.

Conclusion

This is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.

【 授权许可】

   
2014 Plant et al.; licensee BioMed Central Ltd.

【 图 表 】

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