[Frontiers in Bioscience 16, 838-848, January 1, 2011]

Acquired endocrine resistance in breast cancer: implications for tumour metastasis

Edd Hayes1, Robert I Nicholson1, Stephen Hiscox1

1Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff. UK. CF10 3NB

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. The metastatic cascade
3. Acquired endocrine resistance promotes metastatic cell characteristics in preclinical breast cancer cell models
3.1. Modulation of tumour cell adhesion in acquired endocrine resistance
3.1.1. Cell-cell adhesion
3.1.2. Cell-matrix adhesion
4. Changes in cell surface receptor expression in acquired endocrine-resistant breast cancer cells may augment paracrine interactions with the tumour microenvironment
4.1. c-Met receptor
4.2. CD44
5. Elevation of Src kinase activity accompanies acquired endocrine resistance and promotes an in vitro metastatic phenotype
6. Acquired resistance to endocrine agents promotes an angiogenic phenotype
7. Conclusions
8. References

1. ABSTRACT

Endocrine therapy is the treatment of choice in hormone receptor-positive breast cancer. However, the effectiveness of these agents is limited by the development of drug resistance, ultimately leading to disease progression and patient mortality. Whilst pre-clinical cell models of acquired endocrine resistance have demonstrated a role for altered growth factor signalling in the development of an endocrine insensitive phenotype, it is becoming apparent that acquisition of endocrine resistance in breast cancer is also accompanied by the development of an adverse cellular phenotype, with resistant cells exhibiting altered adhesive interactions, enhanced migratory and invasive behaviour, and a capacity to induce angiogenic responses in endothelium. Since invasion and metastasis of cancer cells is a major cause of mortality in breast cancer patients, elucidation of molecular mechanisms underlying the adverse cellular features that accompany acquired endocrine resistance and their subsequent targeting may provide a means of limiting the progression of such tumours in vivo.