Tissue infiltration is different in
desmoid and
fibroma tumours. Both produce high levels of
transforming growth factor beta1 (TGFbeta1), which is related to extracellular matrix (ECM) accumulation which in turn regulates cell function and cell migration. Interactions between
collagen,
proteoglycans and cell surface
fibronectin are involved in the assembly and functions of the ECM. As
toremifene inhibits
collagen and TGFbeta1 synthesis, we tested it in normal,
desmoid and
fibroma fibroblasts. We will report the changes in
glycosaminoglycan (GAG) and
collagen synthesis, TGFbeta1 activity,
fibronectin mRNA expression and TGFbeta1 receptors after
toremifene treatment in normal,
fibroma and
desmoid fibroblasts. We evaluated GAG and
collagen synthesis with 3H-glucosamine and 3H-proline incorporation, TGFbeta1 activity with the ELISA method, TGFbeta1 receptor affinity with 125I-TGFbeta1 binding and total
RNA with Northern blot analysis. GAG and
collagen synthesis, TGFbeta1 activity and
fibronectin levels were higher in
fibroma and
desmoid than normal fibroblasts. The increase was greater in
desmoid than
fibroma tumour cells.
Toremifene treatment reduced GAG and
collagen synthesis, TGFbeta1 activity and
fibronectin levels in all cell cultures. The percentage reduction in GAG was similar in all cultures; the reduction in
collagen synthesis and TGFbeta1 activity was the highest in
desmoid fibroblasts. TGFbeta1 receptors were higher in
fibroma and
desmoid cells than controls.
Toremifene reduced TGFbeta1 receptors only in
desmoid fibroblasts, with no effect on the changes in type I, II, and III receptors. Our data show that
toremifene modifies the ECM components that regulate
cytokine activity and cell migration. The reduction in receptor number only in
desmoid cells suggests that
toremifene may reduce TGFbeta1's affinity for its receptors. Synthesis of a substance regulating
protein kinase activity, which is directly involved in the link between TGFbeta1 and its receptors, cannot be excluded.