The phospholipid analogue hexadecylphosphocholine (HePC) inhibits proliferation of keloid fibroblasts in vitro and modulates their fibronectin and integrin synthesis.
Hexadecylphosphocholine (HePC), a topically effective compound, exerts a strong antiproliferative effect on neoplastic cells. In the present study we investigated (1) the antiproliferative effect of HePC on benign mesenchymal cells in vitro, using as examples normal and keloid fibroblasts, and (2) the influence of HePC on various functional properties of these cells, including phosphatidylcholine biosynthesis, their capacity to reorganize a three-dimensional collagen-I matrix, and their expression and synthesis of fibronectin and subunits of the beta 1 integrin family. Fibroblasts derived from keloids (kelfib) and from normal skin (nfib) were cultured in serum-containing medium and treated in the third passage with 50 mumol/l HePC. Proliferative activity was significantly (P < 0.05) more strongly inhibited in kelfib than in nfib under HePC treatment, whereas their phosphatidylcholine synthesis was inhibited to a similar extent. However, the ability of fibroblasts to contract a three-dimensional collagen-I lattice was significantly (P < 0.05) enhanced only in kelfib treated with HePC. These functional differences following treatment with HePC were paralleled by an upregulation of the alpha 2- and beta 1-integrin chains, and a downregulation of fibronectin synthesis and the alpha 5-subunit. Our results indicate a differential modulation of kelfib metabolism by HePC, suggesting a possible new therapeutic approach for keloid and hypertrophic scars in vivo.
Blume-Peytavi
U
U
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.
Geilen
C C
CC
Sommer
C
C
Almond-Roesler
B
B
Orfanos
C E
CE
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D007627:Keloid / Q000473:pathology*; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012016:Reference Values
D005353:Fibronectins; D016023:Integrins; D010713:Phosphatidylcholines; D010767:Phosphorylcholine; C039128:miltefosine; D003094:Collagen