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Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo
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Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo
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Journal Article
Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo
2012
Overview
Background:
The small stress heat shock protein 27 (Hsp27) has recently turned as a promising target for cancer treatment. Hsp27 upregulation is associated with tumour growth and resistance to chemo- and radio-therapeutic treatments, and several ongoing drugs inhibiting Hsp27 expression are under clinical trial. Hsp27 is now well described to counteract apoptosis and its elevated expression is associated with increased aggressiveness of several primary tumours. However, its role in the later stage of tumour progression and, more specifically, in the later and most deadly stage of tumour metastasis is still unclear.
Methods/results:
In the present study, we showed by qRT–PCR that
Hsp27
gene is overexpressed in a large fraction of the metastatic breast cancer area in 53 patients. We further analysed the role of this protein in mice during bone metastasis invasion and establishment by using Hsp27 genetically depleted MDA-MB231/B02 human breast cancer cell line as a model. We demonstrate that Hsp27 silencing led to reduced cell migration and invasion
in vitro
and that
in vivo
it correlated with a decreased ability of breast cancer cells to metastasise and grow in the skeleton.
Conclusion:
Altogether, these data characterised Hsp27 as a potent therapeutic target in breast cancer bone metastasis and skeletal tumour growth.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Cancer Research UK
Subject
/ Animals
/ Biochemistry, Molecular Biology
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Bone Neoplasms - prevention & control
/ Breast Neoplasms - pathology
/ Diseases of the osteoarticular system
/ Female
/ HSP27 Heat-Shock Proteins - genetics
/ Humans
/ Mice
/ Oncology
/ Patients
/ RNA, Small Interfering - pharmacology
/ Transplantation, Heterologous
/ Tumors
