Biological effects and binding properties of transforming growth factor-beta on human oral squamous cell carcinoma cells.
The effects of transforming growth factor-beta (TGF-beta) on three human oral squamous cell carcinoma cell lines, HSC-2, HSC-3, and HSC-4, were investigated. Although these cell lines were equally sensitive to epidermal growth factor, responses to TGF-beta were variable. Dose-dependent inhibition of cell growth and [3H]thymidine incorporation of HSC-4 were observed by the addition of TGF-beta, whereas growth inhibitory effects on HSC-2 and HSC-3 were marginal. Moreover, treatment of HSC-4 with TGF-beta led to a more than 300-fold increase in fibronectin secretion into the medium. In contrast, TGF-beta did not increase the secretion of fibronectin on HSC-2 and HSC-3. Scatchard analysis of the binding of TGF-beta suggested that all squamous cell carcinoma cell lines have similar binding properties, with two classes of binding sites for TGF-beta. Affinity labeling of 125I-TGF-beta to cell surface receptors revealed the two major affinity crosslinked bands with Mr values of 65 kDa (type I) and 280 kDa (type III). A concomitant loss of 85 kDa band (type II) was observed in all squamous carcinoma cell lines examined. Although the proportions of type I and type III receptors were variable, the type I receptor, which is reported to be the main functional receptor in mediating the TGF-beta action, was commonly observed in these squamous cell carcinoma cell lines. These results indicate that the heterogeneity in response to TGF-beta between cell lines may be due to the difference in the signal transduction pathway of TGF-beta.
Ichijo
H
H
First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
Momose
F
F
Miyazono
K
K
D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D007700:Kinetics; D009062:Mouth Neoplasms; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides / Q000378:metabolism; D015291:Transforming Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D003432:Cross-Linking Reagents; D005353:Fibronectins; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D013388:Succinimides; D015291:Transforming Growth Factors; C019358:disuccinimidyl suberate