Periostin suppression induces decorin secretion leading to reduced breast cancer cell motility and invasion.
The ability of cancer cells to metastasize is dependent on the interactions between their cell-surface molecules and the microenvironment. However, the tumor microenvironment, especially the cancer-associated stroma, is poorly understood. To identify proteins present in the stroma, we focused on phyllodes tumors, rare breast tumors that contain breast stromal cells. We compared the expression of proteins between phyllodes tumor and normal tissues using an iTRAQ-based quantitative proteomic approach. Decorin was expressed at reduced levels in phyllodes tumor tissues, whereas periostin was upregulated; this result was validated by immunohistochemical analysis of phyllodes tumors from 35 patients. Additionally, by immunoprecipitation and mass spectrometry, we confirmed that decorin forms a complex with periostin in both phyllodes tumors and BT-20 breast cancer cells. Following siRNA-mediated knockdown of periostin in T-47D cells, secreted decorin in the culture medium could be detected by multiple reaction monitoring (MRM). Furthermore, periostin knockdown in BT-20 cells and overexpression of decorin in MDA-MB-231 cells inhibited cell motility and invasion. Our results reveal the molecular details of the periostin-decorin complex in both phyllodes tumor tissues and breast cancer cells; this interaction may represent a novel target for anti-cancer therapy.
1] Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU) [2] Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Toshiyuki
T
Ishiba
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Makoto
M
Nagahara
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Tsuyoshi
T
Nakagawa
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Takanobu
T
Sato
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Toshiaki
T
Ishikawa
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Hiroyuki
H
Uetake
Department of Surgical Oncology, Tokyo Medical and Dental University (TMDU).
Kenichi
K
Sugihara
1] Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU) [2] Department of Molecular Diagnosis, Cancer Institute, The Japanese Foundation of Cancer Research (JFCR).
Yoshio
Y
Miki
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU).
Akira
A
Nakanishi
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058575:Decorin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics*
D015815:Cell Adhesion Molecules; D058575:Decorin; C512835:POSTN protein, human