Inhibition of TGF-beta1 suppresses motility and invasiveness of oral squamous cell carcinoma cell lines via modulation of integrins and down-regulation of matrix-metalloproteinases.
Transforming growth factor (TGF)-beta1 is a multifunctional polypeptide that regulates a variety of cellular processes. Several studies have indicated that it is associated with epithelial-mesenchymal transition, angiogenesis, migration and metastases in many types of malignant tumors. We have used a wound-healing assay and a Matrigel invasion assay to evaluate the effects of TGF-beta1 and TGF-beta receptor I kinase inhibitor (TRI) on the cell motility and invasiveness of the human oral squamous cell carcinoma (OSCC) cell lines SAS-L1 and HSC-3. While TGF-beta1 enhanced the migration and invasion of OSCC cells, TRI significantly suppressed the migration and invasion of these cells. Exogenous TGF-beta1 up-regulated the activity of type IV collagenase (gelatinase A and gelatinase B), whereas TRI down-regulated the activity of these matrix metalloproteinases. Western blot analysis revealed that TGF-beta1 enhanced the expression of alpha5, alphav, beta1, beta6 and alphavbeta3 integrin subunits, and these enhanced integrins were down-regulated by treatment with TRI. These results suggest that the inhibition of TGF-beta1 suppresses motility and invasiveness of OSCC cells via modulation of integrins and matrix-metalloproteinases. Therefore, targeting the TGF-beta1 signaling pathway could be beneficial in the treatment of patients with OSCC.
Takayama
Sayaka
S
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo 145-8515, Japan.
Hatori
Masashi
M
Kurihara
Yuji
Y
Kinugasa
Yuriko
Y
Shirota
Tatsuo
T
Shintani
Satoru
S
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D016023:Integrins; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases