Transduction of a mesenchyme-specific gene periostin into 293T cells induces cell invasive activity through epithelial-mesenchymal transformation.
Tumor metastasis is a multistep pathological process involved in the final phase of tumor development. During this process, epithelium-derived tumor cells undergo fibroblast-like transformation, referred to as epithelial-mesenchymal transition (EMT), which contributes to aggressive behavior of tumors. We identify periostin, a mesenchyme-specific gene product, as a contributor to EMT and metastatic potential. Stable expression of a periostin transgene in tumorigenic but non-metastatic 293T cells caused cells to undergo fibroblast-like transformation accompanied by increased expressions of vimentin, epidermal growth factor receptor (EGFR), and matrix metalloproteinase-9. The cells expressing ectopic periostin increased cell migration, invasion, and adhesion by 2-9-fold. Invasive characteristics required signaling through integrin alpha(v)beta5 and EGFR. In addition, periostin-engineered 293T cells formed metastases in immunodeficient mice following either cardiac inoculation or injection into mammary fat pad. These data demonstrate an active role for periostin in EMT and metastasis that requires cross-talk between integrin and EGFR signaling pathways.
Yan
Wei
W
Pioneer Valley Life Sciences Institute, Baystate Medical Center, University of Massachusetts Amherst, Springfield, Massachusetts 01107, USA.
Shao
Rong
R
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019030:Receptors, Vitronectin / Q000378:metabolism; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D016023:Integrins; C512835:POSTN protein, human; C082838:Postn protein, mouse; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D020780:Matrix Metalloproteinase 9