title: Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Altogether, these data characterised Hsp27 as a potent therapeutic target in breast cancer bone metastasis and skeletal tumour growth.
authors.affiliation: Centre de Génétique Moléculaire et Cellulaire, CNRS UMR5534, Université Lyon 1, Université de Lyon, 43 Bd 11 Novembre 1918, 69622 Villeurbanne Cedex, France. benjamin.gibert@lyon.unicancer.fr
authors.forename: B
authors.initials: B
authors.lastname: Gibert
authors.forename: B
authors.initials: B
authors.lastname: Eckel
authors.forename: V
authors.initials: V
authors.lastname: Gonin
authors.forename: D
authors.initials: D
authors.lastname: Goldschneider
authors.forename: J
authors.initials: J
authors.lastname: Fombonne
authors.forename: B
authors.initials: B
authors.lastname: Deux
authors.forename: P
authors.initials: P
authors.lastname: Mehlen
authors.forename: A-P
authors.initials: AP
authors.lastname: Arrigo
authors.forename: P
authors.initials: P
authors.lastname: Clézardin
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Latoud
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000517:prevention & control*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D055551:HSP27 Heat-Shock Proteins; D034741:RNA, Small Interfering