Increased expression and serum levels of the stromal cell-secreted protein periostin in breast cancer bone metastases.
Periostin, a matricellular protein, is overexpressed in the stroma of several cancers. The aim of our study was to investigate more specifically whether periostin expression is associated with bone metastases from breast cancer and to determine its source in the affected bone. Nude mice were inoculated with human MDA-B02 breast cancer cells. Bone metastases-bearing mice were treated with zoledronic acid-an antiresorptive drug-or vehicle. Bone metastases were examined for tumor- and stroma-derived periostin expression by quantitative polymerase chain reaction with human- and mouse-specific primers and immunohistochemistry. Serum periostin and conventional bone turnover markers were also measured. MDA-B02 cells did not express periostin both in vitro and in vivo. However, mouse-derived periostin was markedly overexpressed (eightfold) in metastatic legs compared to noninoculated mice. Serum periostin levels were also markedly increased in metastatic mice and correlated with in situ expression levels. Immunostaining showed that periostin derived from the environing stromal cells of bone metastasis. Bone turnover blockade by zoledronic acid markedly decreased osteolytic lesions but only slightly modulated serum periostin levels. Bone metastases from breast cancer induce overexpression of periostin by surrounding stromal cells. Periostin could be a biochemical marker of the early stromal response associated to breast cancer bone metastasis formation.
Contié
Sylvain
S
Research Unit 664, Institut National de la Santé et de la Recherche Médicale, Lyon, France.
Voorzanger-Rousselot
Nathalie
N
Litvin
Judith
J
Clézardin
Philippe
P
Garnero
Patrick
P
D000595:Amino Acid Sequence; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000235:genetics; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D000077211:Zoledronic Acid
D015815:Cell Adhesion Molecules; D004164:Diphosphonates; D007093:Imidazoles; C512835:POSTN protein, human; D012333:RNA, Messenger; D000077211:Zoledronic Acid