TGF-beta receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes.
This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral keratinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocrine production of TGF-beta appeared unrelated to cellular differentiation. Cells expressed variable proportions of type-I, -II and -III TGF-beta receptors. The expression of type-III receptors correlated inversely with the expression of type-I receptors, but there was no relationship between type-II and either type-I or type-III TGF-beta receptors. Normal cells and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by exogenous TGF-beta 1 and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TGF-beta 1 although it expressed all 3 receptor types. Endogenous TGF-beta was produced by both normal and tumour-derived keratinocytes and correlated inversely to the expression of type-I, but not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF-beta had a diminished response to exogenous TGF-beta 1. The data indicate a complex interaction between the expression of TGF-beta cell-surface receptors, endogenous ligand production and the cellular response to exogenous TGF-beta 1.
Prime
S S
SS
Department of Oral Medicine, Pathology and Microbiology, University of Bristol, UK.
Matthews
J B
JB
Patel
V
V
Game
S M
SM
Donnelly
M
M
Stone
A
A
Paterson
I C
IC
Sandy
J R
JR
Yeudall
W A
WA
D016475:3T3 Cells; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D017077:Culture Media, Conditioned; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007633:Keratins / Q000032:analysis; D051379:Mice; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
D017077:Culture Media, Conditioned; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014746:Vimentin; D007633:Keratins